| 1. |
- Adner, Mikael, et al.
(författare)
-
Contractile endothelin-B (ETB) receptors in human small bronchi
- 1996
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 9:2, s. 351-355
-
Tidskriftsartikel (refereegranskat)abstract
- Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.
|
|
| 2. |
- Adner, Mikael, et al.
(författare)
-
Regional variation in appearance of vascular contractile endothelin-B receptors following organ culture
- 1998
-
Ingår i: Cardiovascular Research. - 1755-3245. ; 37:1, s. 254-262
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the appearance of contractile endothelin (ET)-B receptors following organ culture in different vascular regions. METHOD: The contractile responses of vascular smooth muscle induced by ET-1 and the selective ETB receptor agonist sarafotoxin 6c (S6c) were investigated in circular segments representing eight vascular regions in the rat (aorta, femoral artery, mesenteric artery, branch of the mesenteric artery, proximal and distal parts of the caudal artery, femoral and mesenteric veins). To allow the ETB receptor to be expressed, the segments were placed in organ culture for 1 to 5 days. Pharmacological characterisation of the ET receptors was performed in mesenteric arterial segments. All contractile responses were measured in percentage of K(+)-induced contraction. RESULTS: ET-1 induced strong concentration-dependent contractions of all fresh (not cultured) segments. S6c had negligible effects on all fresh vessels with the exception of the mesenteric vein, where a small contraction was seen. After 1 day of organ culture all tested segments, with the exception of aorta and the proximal part of the caudal artery, showed concentration-dependent contractile responses to S6c which were further augmented after 5 days of culture. The ET-1-induced responses were only slightly affected by organ culture. Contractions induced by S6c were more enhanced in small arteries and veins than in larger arteries. Furthermore, the S6c-induced response was more pronounced in the mesenteric region as compared to the hindlimb. In fresh mesenteric arterial segments FR139317 (ETA receptor antagonist) and bosentan (ETA/ETB receptor antagonist) but not IRL 2500 (ETB receptor antagonist) shifted the ET-1-induced concentration-response curve in parallel to the right. In contrast, after organ culture the S6c-induced concentration-response curves were shifted parallel to the right in the following potency order: IRL 2500 > bosentan > FR139317. CONCLUSION: During normal conditions, the ETA receptor is the dominating mediator of endothelin-induced contraction in eight different vascular regions. Furthermore, this study indicates that most of the vessels have the ability to develop contractile ETB receptors and that this plasticity differs in vascular regions.
|
|
| 3. |
- Nilsson, Daniel, et al.
(författare)
-
Poor reproducibility of allergic rhinitis SNP associations
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e53975-
-
Tidskriftsartikel (refereegranskat)abstract
- Replication of reported associations is crucial to the investigation of complex disease. More than 100 SNPs have previously been reported as associated with allergic rhinitis (AR), but few of these have been replicated successfully. To investigate the general reproducibility of reported AR-associations in candidate gene studies, one Swedish (352 AR-cases, 709 controls) and one Singapore Chinese population (948 AR-cases, 580 controls) were analyzed using 49 AR-associated SNPs. The overall pattern of P-values indicated that very few of the investigated SNPs were associated with AR. Given published odds ratios (ORs) most SNPs showed high power to detect an association, but no correlations were found between the ORs of the two study populations or with published ORs. None of the association signals were in common to the two genome-wide association studies published in AR, indicating that the associations represent false positives or have much lower effect-sizes than reported.
|
|
| 4. |
- Olsson, Petter, et al.
(författare)
-
HealthSWEDE : costs with sublingual immunotherapy - a Swedish questionnaire study
- 2021
-
Ingår i: Allergy, Asthma & Clinical Immunology. - : BMC. - 1710-1484 .- 1710-1492. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy. Methods Primary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients. Results The questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; euro 3907 (SD 4268) vs euro 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, euro 1191 (SD 465) than for reference, euro 751 (SD 589) p < 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, euro 912 (SD 1530), than for reference, euro 3346 (SD 4120) p < 0.001, with presenteeism as main driver. Conclusions SLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations.
|
|
| 5. |
- Papadopoulos, Nikolaos G, et al.
(författare)
-
Research needs in allergy: an EAACI position paper, in collaboration with EFA.
- 2012
-
Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
|
|
| 6. |
- Senti, Gabriela, et al.
(författare)
-
Intralymphatic Immunotherapy : Update and Unmet Needs.
- 2019
-
Ingår i: International Archives of Allergy and Immunology. - : S. Karger. - 1018-2438 .- 1423-0097. ; 178:2, s. 141-149
-
Forskningsöversikt (refereegranskat)abstract
- Allergen-specific immunotherapy (AIT) is the only allergy treatment that confers long-term symptom amelioration for patients suffering from allergy. The most frequently used allergen application route is subcutaneous injection (SCIT), commonly taken as the gold standard, followed by sublingual (SLIT) or oral (OIT) application of allergen preparations. This is an up-to-date review of the clinical evidence for a novel route of allergen application, i.e., directly into lymph nodes - intralymphatic immunotherapy (ILIT). The major advantages of ILIT over the current AIT approaches are its short duration and the low allergen doses administered. The whole treatment consists of merely 3 ultrasound-guided injections into inguinal lymph nodes 1 month apart. While the number of patients included in randomised controlled trials is still limited, the clinical results for ILIT are encouraging, but more clinical trials are needed, as well as more preclinical work for optimising formulations.
|
|
| 7. |
|
|
| 8. |
- Uddman, Rolf, et al.
(författare)
-
Neurotransmitter candidates in the vomeronasal organ of the rat.
- 2007
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 127:9, s. 952-956
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusion: The rich supply of nerve fibres containing neurotransmitters, particularly those containing SP and CGRP, is suggested to be a prerequisite for the recognition of chemical irritants as part of a chemical sense. Objective: The present study was designed to examine the distribution of different neurotransmitter candidates in the vomeronasal organ (VNO) of rats. Materials and methods: The distribution of neurotransmitter candidates was studied in the vomeronasal organ of the rat using immunocytochemistry. Results: The neuronal marker protein gene product 9.5 revealed a very rich supply of nerve fibres within and beneath the sensory epithelium, around blood vessels and glands. A moderate supply of nerve fibres containing tyrosine hydroxylase and neuropeptide Y was mostly seen close to blood vessels. Numerous nerve fibres containing nitric oxide synthase and vasoactive intestinal peptide were seen around blood vessels and in the subepithelial layer, with occasional fibres within the epithelium. Only few fibres located in the subepithelial layer contained pituitary adenylate cyclase activating peptide. Nerve fibres containing substance P and in particular calcitonin gene-related peptide were abundant in and beneath the epithelium and scattered in the submucosal layers around blood vessels.
|
|
| 9. |
- Zhang, Yaping, et al.
(författare)
-
MAPK/NF-kappa B-dependent upregulation of kinin receptors mediates airway hyperreactivity: A new perspective for the treatment
- 2013
-
Ingår i: Pharmacological Research. - : Elsevier BV. - 1096-1186 .- 1043-6618. ; 71, s. 9-18
-
Forskningsöversikt (refereegranskat)abstract
- Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-kappa B) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin receptor upregulation, which is suggested to play an important role in the development of AHR. Environmental risk factors trigger the production of pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) and interleukins (ILs) that activate intracellular MAPK- and NF-kappa B-dependent inflammatory pathways, which subsequently lead to AHR via kinin receptor upregulation. Blockage of intracellular MAPK/NF-kappa B signaling prevents kinin B-1 and B-2 receptor expression in the airways, resulting in a decrease in the response to bradykinin (kinin B-2 receptor agonist) and des-Arg(9)-bradykinin (kinin B-1 receptor agonist). This suggests that MAPK- and NF-kappa B-dependent kinin receptor upregulation can provide a novel option for treatment of AHR in asthmatic as well as in other inflammatory airway diseases. (C) 2013 Elsevier Ltd. All rights reserved.
|
|
| 10. |
|
|
| 11. |
- Andersson, Anders, et al.
(författare)
-
Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes
- 2004
-
Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 138:1, s. 75-82
-
Tidskriftsartikel (refereegranskat)abstract
- CD4(+) and CD8(+) lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8(+) cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4(+) lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4(+) or CD8(+) lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Ralpha) protein were also measured in conditioned medium from human blood CD4(+) and CD8(+) lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Ralpha in conditioned medium from CD4(+) and CD8(+) lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8(+) cytokine IL-16, in the airway lumen, in blood CD4(+) and CD8(+) lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4(+) lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Andiappan, Anand Kumar, et al.
(författare)
-
Investigating highly replicated asthma genes as candidate genes for allergic rhinitis
- 2013
-
Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma genetics has been extensively studied and many genes have been associated with the development or severity of this disease. In contrast, the genetic basis of allergic rhinitis (AR) has not been evaluated as extensively. It is well known that asthma is closely related with AR since a large proportion of individuals with asthma also present symptoms of AR, and patients with AR have a 5-6 fold increased risk of developing asthma. Thus, the relevance of asthma candidate genes as predisposing factors for AR is worth investigating. The present study was designed to investigate if SNPs in highly replicated asthma genes are associated with the occurrence of AR. Methods: A total of 192 SNPs from 21 asthma candidate genes reported to be associated with asthma in 6 or more unrelated studies were genotyped in a Swedish population with 246 AR patients and 431 controls. Genotypes for 429 SNPs from the same set of genes were also extracted from a Singapore Chinese genome-wide dataset which consisted of 456 AR cases and 486 controls. All SNPs were subsequently analyzed for association with AR and their influence on allergic sensitization to common allergens. Results: A limited number of potential associations were observed and the overall pattern of P-values corresponds well to the expectations in the absence of an effect. However, in the tests of allele effects in the Chinese population the number of significant P-values exceeds the expectations. The strongest signals were found for SNPs in NPSR1 and CTLA4. In these genes, a total of nine SNPs showed P-values <0.001 with corresponding Q-values <0.05. In the NPSR1 gene some P-values were lower than the Bonferroni correction level. Reanalysis after elimination of all patients with asthmatic symptoms excluded asthma as a confounding factor in our results. Weaker indications were found for IL13 and GSTP1 with respect to sensitization to birch pollen in the Swedish population. Conclusions: Genetic variation in the majority of the highly replicated asthma genes were not associated to AR in our populations which suggest that asthma and AR could have less in common than previously anticipated. However, NPSR1 and CTLA4 can be genetic links between AR and asthma and associations of polymorphisms in NPSR1 with AR have not been reported previously.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Backer, V., et al.
(författare)
-
Multidisciplinary approaches to identifying and managing global airways disease: Expert recommendations based on qualitative discussions
- 2023
-
Ingår i: Frontiers in Allergy. - : Frontiers Media SA. - 2673-6101. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently co-exist and share pathologic features. Taking a "global" treatment approach benefits diagnosis and treatment of both, but care is often siloed by specialty: joined-up clinics are uncommon. Our objectives were to explore expert opinion to give practical suggestions to identify adults needing global airways care; enhance cross-specialty working; and widen knowledge to support diagnosis and management, integrate with existing care pathways, and supplement existing guidelines.MethodsSixteen practicing physicians from northern Europe were invited for their national and/or international standing in treating asthma and/or chronic rhinosinusitis. Appreciative Inquiry techniques were used to guide their discussions.ResultsKey themes arising were screening and referral, collaboration on management, awareness and education, and research. Provided are screening criteria and suggestions for specialist referrals, and pointers for physicians to optimize their knowledge of global airways disease. Collaborative working is underscored, and practical suggestions are given for multidisciplinary teamworking within global airways clinics. Research gaps are identified.ConclusionThis initiative provides practical suggestions for optimizing the care of adults with CRSwNP and asthma. Discussion of the role of allergy and drug exacerbations on these conditions, and care for patients with other global airways diseases were beyond scope; however, we expect some principles of our discussion will likely benefit patients with related conditions. The suggestions bridge asthma and CRSwNP management guidelines, envisioning interdisciplinary, global airway clinics relevant to various clinical settings. They highlight the value of joint screening for early recognition and referral of patients.
|
|
| 23. |
- Bark, Rusana, et al.
(författare)
-
Sentinel node-assisted neck dissection in advanced oral squamous cell carcinoma - A new protocol for staging and treatment
- 2023
-
Ingår i: Cancer Medicine. - : Wiley-Blackwell. - 2045-7634. ; 12:11, s. 12524-12534
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early-stage T1-T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN-technique in advanced OSCC (T3-T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC.Materials and Methods: In total, 85 patients with T1-T4 OSCC diagnosed 2019-2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT-CT to include all SNs.Results: Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early-stage disease. T3-T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1-T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3-T4 versus T1-T2 (p = 0.0398).Conclusion: SN-assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.
|
|
| 24. |
|
|
| 25. |
- Benson, Mikael, 1954, et al.
(författare)
-
A network-based analysis of the late-phase reaction of the skin.
- 2006
-
Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 118:1, s. 220-5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The late-phase reaction (LPR) of the skin is an in vivo model of allergic inflammation. OBJECTIVE: We sought to identify disease-associated pathways in the LPR using a network-based analysis. METHODS: The LPR was examined by means of DNA microarray analysis of skin biopsy specimens from 10 patients with allergic rhinitis and 10 healthy control subjects. The results were further analyzed in 2 different materials consisting of nasal fluids and allergen-challenged CD4(+) T cells from patients with allergic rhinitis. RESULTS: The DNA microarray analysis revealed several genes of known relevance to allergy. The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot-Leyden crystal protein differed most in expression. A network-based analysis showed upregulation of IL-4- and CCL4-dependent pathways and downregulation of a TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells and chemotactic for eosinophils. We hypothesized that allergen induces release of CCL4 from T(H)2 cells and that this contributes to influx of eosinophils. Further analysis showed increase of CCL4 protein in nasal fluids from allergic patients during the season. Allergen challenge of PBMCs resulted in proliferation of T(H)2 cells and increased production of CCL4 in CD4(+) T cells from allergic patients. An analysis of the DNA microarray data revealed a significant correlation between CCL4 and the eosinophil marker CLC. CONCLUSION: A network-based analysis of the LPR showed increased activity of IL-4- and CCL4- dependent pathways and downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4 from T(H)2 cells might contribute to influx of eosinophils during the LPR. CLINICAL IMPLICATIONS: Involvement of multiple interacting pathways indicates that it might be difficult to identify one single mediator as a biomarker or drug target in allergic inflammation.
|
|
| 26. |
- Benson, Mikael, et al.
(författare)
-
Allergen-reactive antibodies are found in nasal fluids from patients with birch pollen-induced intermittent allergic rhinitis, but not in healthy controls
- 2003
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 58:5, s. 386-392
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased levels of allergen-reactive immunoglobulins (Igs) have been reported in nasal fluids from patients with intermittent allergic rhinitis (IAR) sensitive to ragweed and grass. The aims of this study were to make a detailed characterization of nasal fluid Igs in birch pollen-induced IAR.METHODS: Nasal fluids were obtained from 23 patients with birch pollen-induced IAR during and after the birch pollen season, and from 20 healthy controls. Nasal fluid total and Bet v 1-reactive (IgA), IgE and IgG as well as albumin were analyzed by immunoassays. The integrity of IgA and IgG, and the molecular form of IgA were assessed by Western blotting and column fractionation, respectively.RESULTS: Nasal fluid total IgE and IgG, but not IgA, were higher in patients compared with controls. Western blotting indicated no significant degradation of IgA (including S-IgA) and IgG. Most of the IgA, including Bet v 1-reactive antibodies, was of the secretory form and of the IgA1 subclass. Bet v 1-reactive IgA and IgG were present in all patients, but was mostly nondetectable in controls. No significant differences in the levels of Bet v 1-reactive IgA and IgG were found in patients during the birch pollen season compared with off season. Both Bet v 1 and Bet v 2-reactive IgE were nondetectable in most samples.CONCLUSIONS: Nasal fluid Bet v 1-reactive IgA and IgG were found in all patients with birch pollen-induced IAR, but not in controls. However, no significant differences were found between patients during and after the birch pollen season.
|
|
| 27. |
- Benson, Mikael, 1954, et al.
(författare)
-
Altered levels of the soluble IL-1, IL-4 and TNF receptors, as well as the IL-1 receptor antagonist, in intermittent allergic rhinitis
- 2004
-
Ingår i: Int Arch Allergy Immunol. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 134:3, s. 227-32
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effects of cytokines are modulated by soluble cytokine receptors (SCR) and receptor antagonists. Therefore, allergic disease may depend on altered proportions between cytokines, their SCR and receptor antagonists, rather than absolute changes in cytokine levels. Little is known about SCR in intermittent allergic rhinitis (IAR). OBJECTIVE: To examine the concentrations of SCR, i.e. sIL-1R2, sIL-4R, sIL-6R and sTNFR1, as well as the interleukin-1 receptor antagonist (IL-1Ra) in nasal fluids from allergen-challenged patients with IAR and healthy controls. METHODS: 30 patients with birch- or grass-pollen-induced IAR and 30 healthy controls were studied. In the patients nasal fluids were obtained before as well as 1 and 6 h after allergen provocation. RESULTS: Both symptom scores and rhinoscopic signs of rhinitis increased in the patients after allergen challenge. Comparisons between patients and controls showed that sIL-4R was lower in patients before and 1 and 6 h after provocation. IL-1Ra was lower before and 1 h after provocation. In addition, lower concentrations of sTNFR1 were found in patients after 1 h, while sIL-1R2 concentrations were higher after 1 h. Comparisons of patients before and after challenge showed that IL-1Ra and sTNFR1 decreased after 1 h, while sIL-1R2 increased. No significant differences were found compared to 6 h. sIL-6R did not significantly differ between the study groups. CONCLUSIONS: After allergen challenge, significant changes in the nasal fluid levels of IL-1Ra, sIL-1R2 and sTNFR1 were found. By contrast, sIL-4R remained at lower levels than in controls both before and after challenge. Since sIL-4R modulates IgE synthesis, this may play a role in the pathogenesis of IAR.
|
|
| 28. |
- Benson, Mikael, 1954, et al.
(författare)
-
Connectivity can be used to identify key genes in DNA microarray data: a study based on gene expression in nasal polyps before and after treatment with glucocorticoids
- 2007
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 127:10, s. 1074-1079
-
Tidskriftsartikel (refereegranskat)abstract
- Conclusions. The presented analysis of nasal polyposis using connectivity based on the PubGene literature co-citation network demonstrates that this tool can be used to identify key genes in DNA microarray studies of human polygenic diseases. Objectives. DNA microarray studies of complex diseases may reveal differential expression of hundreds of genes. According to network theory and studies of yeast cells, genes that are connected with several other genes appear to have key regulatory roles. This study aimed to examine if this principle can be translated to DNA microarray studies of human disease, using nasal polyposis as a base for the analysis. Materials and methods. The connectivity of differentially expressed genes from a previously described microarray study of nasal polyposis before and after treatment with glucocorticoids was determined. This was done using the literature co-citation network PubGene. Results. In all, 166 genes were differentially expressed; 39 of these were previously defined as inflammatory and considered important for nasal polyposis. The connectivity of all differentially expressed genes was analysed using the PubGene literature co-citation network. Seventy-four of the 166 genes were connected to other genes. By contrast, the average number of connected genes among 100 sets of 166 randomly chosen genes was 31.5. A small number of the differentially expressed genes were highly connected, while most genes had few or no connections. This indicated a scale-free network. The most connected gene was interleukin-8, an inflammatory gene of known importance for nasal polyposis. Twenty-eight of the 74 connected genes were inflammatory (38%), compared with 11 of the 92 unconnected genes (12%), p < 0.0001. Since most evidence suggests that nasal polyps are inflammatory in their nature, this supports the hypothesis that connected genes have more disease relevance than unconnected genes.
|
|
| 29. |
- Benson, Mikael, 1954, et al.
(författare)
-
DNA microarray analysis of chromosomal susceptibility regions to identify candidate genes for allergic disease: A pilot study
- 2004
-
Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 124:7, s. 813-819
-
Tidskriftsartikel (refereegranskat)abstract
- Objective-To examine whether DNA microarray analysis of chromosomal susceptibility regions for allergy can help to identify candidate genes. Material and Methods-Nasal biopsies were obtained from 23 patients with allergic rhinitis and 12 healthy controls. RNA was extracted from the biopsies and pooled into three patient and three control pools. These were then analysed in duplicate with DNA microarrays containing 12626 genes. Candidate genes were further examined in nasal biopsies (real-time polymerase chain reaction) and blood samples (single nucleotide polymorphisms) from other patients with allergic rhinitis and from controls. Results-A total of 37 differentially expressed genes were identified according to criteria involving both the size and consistency of the gene expression levels. The chromosomal location of these genes was compared with the chromosomal susceptibility regions for allergic disease. Using a statistical method, five genes were identified in these regions, including serine protease inhibitor, Kazal type, 5 (SPINK5) and HLA-DRB2. The relevance of these genes was examined in other patients with allergic rhinitis and in controls; none of the genes were differentially expressed in nasal biopsies. Moreover, no association between allergic rhinitis and SPINK5 polymorphisms was found, at either the genotype or haplotype level. Conclusions-DNA microarray analysis of chromosomal susceptibility regions did not lead to identification of candidate genes that could be validated in a new material. However, because gene polymorphisms may cause differential gene expression, further studies, including validation data, are needed to examine this approach.
|
|
| 30. |
|
|
| 31. |
- Benson, Mikael, 1954, et al.
(författare)
-
DNA microarray analysis of transforming growth factor-β and related transcripts in nasal biopsies from patients with allergic rhinitis
- 2002
-
Ingår i: Cytokine. ; 18:1, s. 20-25
-
Tidskriftsartikel (refereegranskat)abstract
- Decreased activity of anti-inflammatory cytokines like transforming growth factor (TGF)-β may contribute to allergic inflammation. In vivo effects of TGF-β-effects are difficult to infer from local concentrations, since TGF-β-effects depend on a complex system of regulatory proteins and receptors. Instead the effects of TGF-β might be inferred by examining TGF-β-inducible transcripts. In this study DNA microarrays were used to examine local expression of TGF-β, TGF-β-regulatory and -inducible transcripts in nasal biopsies from patients with symptomatic allergic rhinitis and healthy controls. In addition, nasal fluids were analysed with cytological and immunological methods. Nasal fluid eosinophils, albumin, eosinophil granulae proteins and IgE, but not TGF-β, were higher in patients than in controls. DNA microarray analysis of nasal mucosa showed expression of transcripts encoding TGF-β, TGF-β-regulatory proteins and -receptors at variable levels in patients and controls. By comparison, analysis of 28 TGF-β-inducible transcripts indicated that 23 of these had lower measurement values in patients than in controls, while one was higher, and the remaining four were absent in both patients and controls. In summary, TGF-β and a complex system of regulatory genes and receptors are expressed in the nasal mucosa. Low expression of TGF-β-inducible transcripts may indicate decreased TGF-β activity in allergic rhinitis. DNA microarray analysis may be a way to study cytokine effects in vivo.
|
|
| 32. |
- Benson, Mikael, 1954, et al.
(författare)
-
DNA microarrays to study gene expression in allergic airways.
- 2002
-
Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894 .- 1365-2222. ; 32:2, s. 301-8
-
Tidskriftsartikel (refereegranskat)abstract
- Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample.
|
|
| 33. |
|
|
| 34. |
- Benson, Mikael, 1954, et al.
(författare)
-
Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis
- 2005
-
Ingår i: Clin Exp Allergy. - : Wiley. ; 35:4, s. 473-478
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample. OBJECTIVE: To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls. METHODS: Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.
|
|
| 35. |
- Benson, Mikael, 1954, et al.
(författare)
-
Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps.
- 2004
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 113:6, s. 1137-43
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.
|
|
| 36. |
- Benson, Mikael, 1954, et al.
(författare)
-
Increased expression of Vascular Endothelial Growth Factor-A in seasonal allergic rhinitis.
- 2002
-
Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 20:6, s. 268-73
-
Tidskriftsartikel (refereegranskat)abstract
- Increased vascular dilatation and permeability characterize allergic rhinitis. In this study oligonucleotide microarrays (Affymetrix HuGe95A) were used to identify differentially expressed vasoactive genes in nasal biopsies from 23 patients with symptomatic seasonal allergic rhinitis (SAR) and 12 healthy controls. RNA was extracted from the biopsies and pooled in three patient and three control pools. Out of 12,626 analysed transcripts, 39 were higher and 81 lower in the patients. Of these transcripts two have vasoactive effects: Vascular Endothelial Growth Factor-A (VEGF-A) and the Beta-1-Adrenergic Receptor. Both were higher in patients than in controls. The mean +/- SEM expression levels in arbitrary units of VEGF-A were 130 +/- 123 in the patients and 59 +/- 53 in the controls. The fold ratio in expression levels between patients/controls was 2.2. The corresponding values for the beta-1-adrenergic receptor were 129 +/- 123 in the patients and 40 +/- 31 in the controls. The fold ratio between patient/controls was 3.2. The role of VEGF-A was assessed by determining VEGF-A concentrations in nasal fluids from another 30 patients with SAR before and after allergen provocation. VEGF-A increased from 124.3 +/- 30.2 to 163.2 +/- 37.8 pg/ml after challenge, P < 0.05. In summary, oligonucleotide microarray analysis of nasal biopsies and protein analyses of nasal fluids indicate that VEGF-A may be an important mediator in SAR.
|
|
| 37. |
- Benson, Mikael, 1954, et al.
(författare)
-
Inverse relation between nasal fluid Clara Cell Protein 16 levels and symptoms and signs of rhinitis in allergen-challenged patients with intermittent allergic rhinitis.
- 2007
-
Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 62:2, s. 178-83
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Decreased levels of the anti-inflammatory Clara Cell Protein 16 (CC16) are found in intermittent allergic rhinitis (IAR) and asthma. In asthma this decrease has been associated with hyperreactivity and the A38G single nucleotide polymorphism (SNP). The aim of this study was to examine if IAR is associated with signs and symptoms of rhinitis and the A38G SNP. METHODS: Nasal fluid CC16 was analyzed in 20 patients with IAR before allergen challenge and 1 and 6 h after challenge, and from 28 healthy controls. The A38G SNP was analyzed in 80 patients with IAR and 106 controls. Nasal biopsies were obtained from three subjects in each group for immunohistochemical analysis of CC16. RESULTS: In the allergen-challenged patients symptoms and rhinoscopic signs of rhinitis increased after 1 h and normalized after 6 h. In contrast, nasal fluid CC16 decreased 1 h after allergen challenge and returned to baseline after 6 h. Nasal fluid CC16 levels did not differ from controls before and 6 h after challenge. Immunohistochemical investigation showed intense CC16 staining in the nasal epithelium of both patients before season and healthy controls, but weak staining in symptomatic patients during season. No significant association between the A38G SNP and IAR was found. CONCLUSION: There was an inverse relation between nasal fluid CC16 levels and symptoms and signs of rhinitis in allergen-challenged patients with IAR. However, there was no association between IAR and the A38G SNP.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Benson, Mikael, et al.
(författare)
-
Systembiologin kan förändra sjukvården radikalt. Ger underlag för individualiserad prediktion, prevention och behandling : [Systems biology can radically change health care. Basis for individualized prediction, prevention and treatment]
- 2007
-
Ingår i: Läkartidningen. - : Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:42, s. 3037-3041
-
Tidskriftsartikel (refereegranskat)abstract
- Vanliga sjukdomar som allergi, diabetes och cancer är komplexa, dvs de beror på obalans mellan ett stort antal gener och miljöfaktorer, snarare än på enskilda »felande« gener. Det finns teknik för att samtidigt analysera mRNA- och proteinuttryck för alla människans gener. Detta har resulterat i väldiga datamängder, som kan bidra till att öka förståelsen av komplexa sjukdomar. Problemet är att strukturera och tolka informationen.Systembiologi syftar till att konstruera ett teoretiskt ramverk för att beskriva hur molekylära signalvägar och nätverk, snarare än enskilda molekyler, orsakar sjukdom. Detta har börjat ge kliniska resultat, tex individualiserad medicinering vid behandling av cancer.Inom de närmsta decennierna förutspås systembiologisk forskning få klinisk betydelse, inte bara för att individualisera behandling, utan även för att förutsäga eller förebygga sjukdomar. Läkemedelsindustrin gör också stora systembiologiska satsningar för att utveckla nya mediciner.Det är därför angeläget att svenska kliniker, forskare och beslutsfattare snarast tar ställning till hur klinisk systembiologisk forskning ska bedrivas i Sverige.I denna artikel ges en introduktion till nya tekniker för att samtidigt studera människans alla gener. Dessutom beskrivs systembiologiska principer för att tolka resultaten och vilka kliniska konsekvenser detta kan få.
|
|
| 42. |
|
|
| 43. |
- Bogefors, Jesper, et al.
(författare)
-
LEAP-2, LL-37 and RNase7 in tonsillar tissue: downregulated expression in seasonal allergic rhinitis.
- 2014
-
Ingår i: Pathogens and Disease. - 2049-632X. ; 72:1, s. 55-60
-
Tidskriftsartikel (refereegranskat)abstract
- In the upper airway, the production of antimicrobial peptides (AMPs) protects against bacteria, viruses and fungi. Previous investigations have revealed downregulated expression of AMPs in different manifestations of allergic disease. In this study, we examined the expression of LL-37, RNase7 and LEAP-2 in tonsillar tissue and studied a possible relation to seasonal allergic rhinitis (SAR).
|
|
| 44. |
- Bogefors, J., et al.
(författare)
-
Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?
- 2010
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 65:10, s. 1222-1226
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited.AIM OF THE STUDY: To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season.METHODS: The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium.RESULTS: Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups.CONCLUSION: Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease.
|
|
| 45. |
- Bogefors, Jesper, et al.
(författare)
-
Reduced tonsillar expression of human β-defensin 1, 2 and 3 in allergic rhinitis.
- 2012
-
Ingår i: FEMS Immunology and Medical Microbiology. - 1574-695X. ; 65:3, s. 431-438
-
Tidskriftsartikel (refereegranskat)abstract
- Airway infections are known to cause exacerbations of allergy and asthma. Tonsils constitute a primary site for microbial recognition and triggering of the immune system in the airways. Human β-defensins (HBDs) are antimicrobial peptides with an important role in this defense. Our aim was to investigate HBD1-3 in tonsillar tissue and their potential role in allergic rhinitis (AR). Tonsils, obtained from patients with AR and non-allergic controls, and isolated tonsillar CD4(+) , CD8(+) and CD19(+) lymphocytes were analyzed for HBD1-3 expression using real-time RT-PCR and/or immunohistochemistry. Tonsillar tissue, mixed tonsillar lymphocytes and airway epithelial cells (AECs) were cultured with or without IL-4, IL-5, IL-13 or histamine followed by measurements of HBD1-3 release using ELISA. HBD1-3 were present in tonsillar tissue, including epithelial, CD4(+) , CD8(+) and CD19(+) cells. The expression was reduced in allergic compared to healthy tonsils. Stimulation of AECs with IL-4, IL-5 and histamine down-regulated the HBD release, whereas no effects were seen in cultured tonsils or lymphocytes. This study demonstrates presence of HBD1-3 in tonsils and that the levels are reduced in patients with AR. Together with the down-regulation of HBDs in epithelial cells in the presence of allergic mediators suggest that AR patients have an impaired antimicrobial defense that might make them more susceptible to respiratory tract infections. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
|
|
| 46. |
- Bogefors, Jesper, et al.
(författare)
-
Retinoic acid-inducible gene 1-like receptors in the upper respiratory tract.
- 2011
-
Ingår i: American Journal of Rhinology & Allergy. - : SAGE Publications. - 1945-8924 .- 1945-8932. ; 25:6, s. 262-267
-
Tidskriftsartikel (refereegranskat)abstract
- Retinoic acid-inducible gene 1-like receptors (RLRs) are a novel family of pattern recognition receptors that include retinoic acid-inducible gene 1 (RIG-1), melanoma differentiation-associated gene 5 (MDA-5), and laboratory of genomics and physiology 2 (LGP-2). The knowledge of RLRs and their function in the human airway is limited. This study explores the role of RLRs in the upper respiratory tract.
|
|
| 47. |
- Bogefors, Jesper, et al.
(författare)
-
Upregulated levels of human β-defensins in patients with seasonal allergic rhinitis after allergen-specific immunotherapy treatment.
- 2013
-
Ingår i: International Forum of Allergy & Rhinology. - : Wiley. - 2042-6984 .- 2042-6976. ; 3:2, s. 99-103
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antimicrobial peptides (AMPs) are important actors in the innate immune system. One class of AMPs is the human β-defensins (HBDs), a group of small peptides with a broad spectrum of antimicrobial activities. Expression of HBDs is downregulated in different manifestations of allergic disease. In this study, we examine whether allergen-specific immunotherapy (ASIT) affects the nasal levels of HBDs in patients with seasonal allergic rhinitis (SAR). METHODS: Nasal biopsies were examined for the occurrence of HBD1-3 with real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Nasal lavage (NAL) fluids from healthy individuals, untreated SAR patients and SAR patients before and after ASIT were analyzed for levels of HBD1-3 using enzyme-linked immunosorbent assay (ELISA). RESULTS: Examination of nasal biopsies revealed HBD1-3 expression at gene level as well as at protein level in all samples tested. HBD1 and HBD3 messenger RNA (mRNA) levels were downregulated in SAR patients compared to healthy individuals. All HBDs were found in NAL fluids. SAR patients having completed 3 years of ASIT displayed higher levels of HBD1 and HBD2 than before treatment, whereas levels of HBD3 were unaffected. CONCLUSION: The present study demonstrates an upregulation of HBD1 and HBD2 in SAR patients after completion of ASIT. This may reflect the importance of an intact innate immune response as part of our defense against infections among allergic individuals.
|
|
| 48. |
- Bryborn, Malin, et al.
(författare)
-
Comprehensive evaluation of genetic variation in S100A7 suggests an association with the occurrence of allergic rhinitis.
- 2008
-
Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 9:Mar 28
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: S100A7 is a calcium-binding protein with chemotactic and antimicrobial properties. S100A7 protein levels are decreased in nasal lavage fluid from individuals with ongoing allergic rhinitis, suggesting a role for S100A7 in allergic airway inflammation. The aims of this study were to describe genetic variation in S100A7 and search for associations between this variation and allergic rhinitis. METHODS: Peripheral blood was collected from 184 atopic patients with a history of pollen-induced allergic rhinitis and 378 non-atopic individuals, all of Swedish origin. DNA was extracted and the S100A7 gene was resequenced in a subset of 47 randomly selected atopic individuals. Nine polymorphisms were genotyped in 184 atopic and 378 non-atopic individuals and subsequently investigated for associations with allergic rhinitis as well as skin prick test results. Haplotypes were estimated and compared in the two groups. RESULTS: Thirteen polymorphisms were identified in S100A7, of which 7 were previously undescribed. rs3014837 (G/C), which gives rise to an Asp --> Glu amino acid shift, had significantly increased minor allele frequency in atopic individuals. The major haplotype, containing the major allele at all sites, was more common in non-atopic individuals, while the haplotype containing the minor allele at rs3014837 was equally more common among the atopic individuals. Additionally, heterozygotes at this site had significantly higher scores in skin prick tests for 9 out of 11 tested allergens, compared to homozygotes. CONCLUSION: This is the first study describing genetic variation, associated with allergy, in S100A7. The results indicate that rs3014837 is linked to allergic rhinitis in our Swedish population and render S100A7 a strong candidate for further investigations regarding its role in allergic inflammation.
|
|
| 49. |
- Bryborn, Malin, et al.
(författare)
-
Differentiated S100A7 expression in infected tonsils and tonsils from allergic individuals.
- 2008
-
Ingår i: Pathogens and Disease. - 2049-632X. ; 53:3, s. 413-420
-
Tidskriftsartikel (refereegranskat)abstract
- Palatine tonsils are continuously exposed to microorganisms and antigens and secrete antimicrobial peptides as a first line of defense. S100A7 is a protein with antimicrobial and chemotactic properties. Our aim was to investigate how the expression of S100A7 in human palatine tonsils is affected by inflammatory processes. Tonsils obtained from 109 patients undergoing tonsillectomy were divided into groups of infected and noninfected as well as allergic and nonallergic, based on the results from tonsillar core culture tests and Phadiatop analysis, respectively. Western blot and immunohistochemistry were used to assess protein expression and real-time PCR was used to quantify mRNA levels. To explore the induction of S100A7, tonsils were stimulated with lipopolysaccharide in vitro. The immunohistochemical staining for S100A7 was most intense in the tonsillar epithelium, but the protein was also detected in B- and T-cell regions, which was confirmed with Western blot on isolated B and T cells. The S100A7 expression appeared to be the highest in CD8(+) T cells. Reduced mRNA levels of S100A7 were detected in infected tonsils as well as in tonsils from allergic individuals. In vitro stimulation of tonsils with lipopolysaccharide did not have any effect on the expression. The results suggest a role for S100A7 in recurrent tonsillitis and allergic disease.
|
|
| 50. |
|
|
