| 1. |
- Bogefors, Jesper, et al.
(författare)
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LEAP-2, LL-37 and RNase7 in tonsillar tissue: downregulated expression in seasonal allergic rhinitis.
- 2014
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Ingår i: Pathogens and Disease. - 2049-632X. ; 72:1, s. 55-60
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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).
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| 2. |
- Bogefors, J., et al.
(författare)
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Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?
- 2010
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley-Blackwell. - 0105-4538 .- 1398-9995. ; 65:10, s. 1222-1226
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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.
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| 3. |
- Bogefors, Jesper, et al.
(författare)
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Reduced tonsillar expression of human β-defensin 1, 2 and 3 in allergic rhinitis.
- 2012
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Ingår i: FEMS Immunology and Medical Microbiology. - 1574-695X. ; 65:3, s. 431-438
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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.
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| 4. |
- Bogefors, Jesper, et al.
(författare)
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Retinoic acid-inducible gene 1-like receptors in the upper respiratory tract.
- 2011
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Ingår i: American Journal of Rhinology & Allergy. - : SAGE Publications. - 1945-8924 .- 1945-8932. ; 25:6, s. 262-267
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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.
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| 5. |
- Bogefors, Jesper, et al.
(författare)
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Upregulated levels of human β-defensins in patients with seasonal allergic rhinitis after allergen-specific immunotherapy treatment.
- 2013
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Ingår i: International Forum of Allergy & Rhinology. - : Wiley. - 2042-6984 .- 2042-6976. ; 3:2, s. 99-103
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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.
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| 6. |
- Bryborn, Malin, et al.
(författare)
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Differentiated S100A7 expression in infected tonsils and tonsils from allergic individuals.
- 2008
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Ingår i: Pathogens and Disease. - 2049-632X. ; 53:3, s. 413-420
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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.
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| 7. |
- Månsson, Anne, et al.
(författare)
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A distinct Toll-like receptor repertoire in human tonsillar B cells, directly activated by PamCSK, R-837 and CpG-2006 stimulation.
- 2006
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 118:Jun 16, s. 539-548
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptors (TLRs) recognize specific pathogen-associated molecular patterns (PAMPs), which subsequently trigger innate immunity. Recent data also suggest a role for TLRs in the direct activation of adaptive immune cells. In the present study, the expression and function of TLR1-TLR10 were characterized in purified human tonsillar B cells, focusing on differences among CD19(+) CD38(-) CD27(-) (naive B cells), CD19(+) IgD(-) CD27- [germinal centre (GC) B cells] and CD19(+) CD38(-)CD27(+) (memory B cells) cells. The study was also designed to compare the TLR expression in B cells obtained from infected and hyperplastic tonsils that served as controls. The results demonstrated a distinct repertoire of TLRs, in which TLR1, TLR2, TLR7, TLR9 and TLR10 predominated. No differences were found among naive, GC and memory B cells. Tonsillar infection did not substantially alter the TLR expression profile in ex vivo-isolated B-cell subsets. Purified CD19+ B cells stimulated with Pam(3)CSK(4), R-837 and CpG oligodeoxynucleotide (ODN) 2006, via TLR1/TLR2, TLR7 and TLR9, respectively, showed an induction of interleukin-6 secretion and an up-regulated expression of human leucocyte antigen (HLA)-DR. Collectively, the present study demonstrates that B cells exhibit constitutively high levels of specific TLRs, which are not developmentally regulated during the B-cell differentiation process. Ongoing microbial infections, such as chronic tonsillitis, do not appear to affect the TLR profile in B cells. Furthermore, the distinct expression of TLRs allows B cells to.respond directly to the cognate PAMPs. This further emphasizes the role of TLRs in directly activating adaptive immune cells.
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| 8. |
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| 9. |
- Månsson, Anne, et al.
(författare)
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Nasal CpG oligodeoxynucleotide administration induces a local inflammatory response in nonallergic individuals.
- 2009
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64, s. 1292-1300
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously demonstrated the presence of toll-like receptor 9 in the nasal mucosa of both healthy and allergic individuals. CpG motifs, found in bacterial and viral DNA, elicit strong immunostimulatory effects via this receptor. CpG is known to skew the immune system towards a T helper 1 (Th1) profile, thereby suppressing Th2-driven allergic responses. This study was designed to examine the effects of CpG administration in the human nose. Methods: Twenty subjects, of whom 10 suffered from seasonal allergic rhinitis (AR), were challenged intranasally with CpG outside pollen season. Symptom scores, nasal airway resistance (NAR), and nasal and pulmonary nitric oxide (NO) levels were assayed prior to challenge and 30 min, 6, 24 and 48 h post challenge. The presence of leukocytes and various cytokines were analyzed in nasal lavage (NAL) fluids before and after CpG exposure. Results: Increased NAR, nasal NO production and secretion of interleukin (IL)-1beta, IL-6, and IL-8 were seen after CpG exposure. Further analysis revealed that this inflammatory response was more marked in healthy subjects than among patients with AR, although a higher basal inflammatory response was recorded in the allergic group. In vitro experiments suggest that the effects induced by CpG are mediated by epithelial cells and neutrophils. Conclusion: Nasal administration of CpG induces a local airway inflammation, more distinct among healthy than allergic individuals. The reduced responsiveness to CpG in allergic patients might be related to the ongoing minimal persistent inflammation. Results from cytokine analyses reflect the ability of CpG to induce a pro-inflammatory Th1-like immune response.
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| 10. |
- Månsson, Anne, et al.
(författare)
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NOD-like receptors in the human upper airways: a potential role in nasal polyposis.
- 2011
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 66, s. 621-628
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Tidskriftsartikel (refereegranskat)abstract
- To cite this article: Månsson A, Bogefors J, Cervin A, Uddman R, Cardell LO. NOD-like receptors in the human upper airways: a potential role in nasal polyposis. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02527.x. ABSTRACT: Background: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are newly discovered cytosolic receptors belonging to the pattern-recognition receptor family. They detect various pathogen-associated molecular patterns, triggering an immune response. The knowledge about these receptors, and their role in health and disease, is limited. The aim of the present study was to characterize the expression of NOD1, NOD2, and NALP3 in the human upper airways. Methods: Surgical samples were obtained from patients with tonsillar disease (n = 151), hypertrophic adenoids (n = 9), and nasal polyposis (n = 24). Nasal biopsies were obtained from healthy volunteers (n = 10). The expression of NOD1, NOD2, and NALP3 was analyzed using real-time PCR and immunohistochemistry. Results: Expression of NOD1, NOD2, and NALP3 mRNA and protein were seen in all tissue specimens. The NLR mRNA was found to be higher in nasal polyps than in normal nasal mucosa, and local steroid treatment reduced the NLR expression in polyps. In contrast, tonsillar infection with Streptococcus pyogenes or Haemophilus influenzae did not affect the NLR expression. Conclusions: The present study demonstrates the presence of NLRs in several upper airway tissues and highlights a potential role of NLRs in chronic rhinosinusitis with polyps.
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