| 96271. |
- Bossini-Castillo, Lara, et al.
(author)
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Confirmation of association of the macrophage migration inhibitory factor gene with systemic sclerosis in a large European population.
- 2011
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 50, s. 1976-1981
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Journal article (peer-reviewed)abstract
- Objectives. The aim of this study was to confirm the implication of macrophage migration inhibitory factor (MIF) gene in SSc susceptibility or clinical phenotypes in a large European population.Methods. A total of 3800 SSc patients and 4282 healthy controls of white Caucasian ancestry from eight different European countries were included in the study. The MIF -173 single nucleotide polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5' allelic discrimination assay.Results. The MIF -173 SNP showed association with SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF -173 polymorphism according to SSc clinical phenotype revealed that the frequency of the -173*C allele was significantly higher in the dcSSc group compared with controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency of the MIF -173*C allele was significantly underrepresented in the lcSSc group compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86, 95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR = 0.83, 95% CI 0.73, 0.94)].Conclusion. Our results confirm the role of MIF -173 promoter polymorphism in SSc, and provide evidence of a strong association with the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a promising clinical phenotype genetic marker.
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| 96272. |
- Bossini-Castillo, Lara, et al.
(author)
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KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor
- 2012
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 14:6
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Journal article (peer-reviewed)abstract
- Introduction: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.
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| 96273. |
- Bossios, Apostolos, 1969, et al.
(author)
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IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome.
- 2009
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In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; :Nov 26
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Journal article (peer-reviewed)abstract
- To cite this article: Bossios A, Sjöstrand M, Dahlborn A-K, Samitas K, Malmhäll C, Gaga M, Lötvall J. IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome. Allergy 2009. DOI: 10.1111/j.1398-9995.2009.02271.x.Abstract Background: Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease. Methods: CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed. Results: Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma. Conclusion: CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.
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| 96274. |
- Bossios, Apostolos, 1969, et al.
(author)
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Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release.
- 2008
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In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 38:10, s. 1615-26
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Journal article (peer-reviewed)abstract
- BACKGROUND: Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved. OBJECTIVE: To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro. METHODS: BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor kappaB (NF-kappaB) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-gamma-induced protein (IP)-10/CXCL10, IFN-lambda1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured. RESULTS: RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-kappaB translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-kappaB translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8. CONCLUSION: HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations.
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| 96275. |
- Bossmar, Thomas, et al.
(author)
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Expression of the oxytocin gene, but not the vasopressin gene, in the rat uterus during pregnancy: influence of oestradiol and progesterone
- 2007
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In: Journal of Endocrinology. - : Bioscientifica. - 1479-6805 .- 0022-0795. ; 193:1, s. 121-126
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Journal article (peer-reviewed)abstract
- Oxytocin (OT) and vasopressin (VP) are neurohypophyseal hormones with potent stimulatory actions on the uterus. In order to determine whether these hormones may have a paracrine action on the uterus, OT and VP gene expression was studied in myometrium from pregnant rats at gestational ages of 14 and 20 days, and from ovariectomized animals treated with oestradiol and progesterone. OT and VP mRNA concentrations were measured using real-time quantitative reverse transcription-PCR, and OT- and VP-like immunoreactivities were determined using RIA. OT mRNA was detected in the uterus from pregnant rats, but did not differ between the groups of different gestational ages. Oestradiol significantly (P<0.05) stimulated OT gene expression in ovariectomized rats. Progesterone alone was without effect on OT mRNA concentrations, but significantly (P<0.05) reduced the oestradiol-induced OT mRNA accumulation. The OT-like immunoreactivity in an extract of myometrium from pregnant rats was eluted from a reverse-phase HPLC column with a retention time identical to that of synthetic OT. Neither VP mRNA nor VP-like immunoreactivity was detected in the myometrium from pregnant or ovariectomized rats. The study demonstrates steroid-dependent expression of the OT gene in the rat uterus and processing of uterine preprooxytocin to the mature nonapeptide. The data support the theory that this peptide may act in a paracrine pathway. No evidence was found for the presence of VP in the uterus so that, if the hormone is involved in a stimulatory action on this tissue, it probably acts via an endocrine mechanism.
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| 96276. |
- Bossmar, Thomas
(author)
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OXYTOCIN AND VASOPRESSIN IN UTERINE ACTIVITY. Receptor-mediated agonism and antagonism with special regard to the aetiology and treatment of preterm labour and primary dysmenorrhoea.
- 1996
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Doctoral thesis (other academic/artistic)abstract
- With a view to the aetiology and treatment of preterm labour and primary dysmenorrhoea we studied the influence of sexual steroids on the plasma levels of oxytocin and vasopressin, effect of these peptides on uterine contractility in vitro and in vivo, receptor concentrations and antagonists to oxytocin and vasopressin. In postmenopausal women oestrogen increased the concentrations in plasma of both peptides, whereas progesterone increased oxytocin but decreased vasopressin levels. In pregnant women no increase in oxytocin or vasopressin V1a receptors was seen at the onset of labour and concentrations did not differ between women delivered preterm or at term. In advanced labour the oxytocin receptor decreased. Inhibition in vitro of the antagonist 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin correlated to the concentration of the oxytocin receptor. Vasopressin had a higher effect than oxytocin in non-pregnant women, particularly before menstruation. In both pregnant and non-pregnant state, myometrial effects and receptor-concentrations to oxytocin correlated, but not those to vasopressin. SR 49059 inhibited vasopressin-induced myometrial activity in vitro and in women during menstruation. Up-regulation of oxytocin receptors does not seem to cause the start of labour preterm or at term, but a down-regulation by oxytocin itself may occur. Oxytocin acts specifically via its own receptor whereas vasopressin acts via both receptors. The findings regarding 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin supports its therapeutic action in preterm labour and a role for oxytocin in the onset of labour. SR 49059 is a selective V1a receptor antagonist and may be a valuable tool for studying the role of vasopressin in the mechanisms of primary dysmenorrhoea.
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| 96277. |
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| 96278. |
- Bosson, Jenny A, et al.
(author)
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Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation
- 2013
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12
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Journal article (peer-reviewed)abstract
- BACKGROUND: Ozone concentrations are predicted to increase over the next 50 years due to global warming and the increased release of precursor chemicals. It is therefore urgent that good, reliable biomarkers are available to quantify the toxicity of this pollutant gas at the population level. Such a biomarker would need to be easily performed, reproducible, economically viable, and reflective of ongoing pathological processes occurring within the lung.METHODOLOGY: We examined whether blood neutrophilia occurred following a controlled ozone challenge and addressed whether this could serve as a biomarker for ozone-induced airway inflammation. Three separate groups of healthy subjects were exposed to ozone (0.2 ppm, 2h) and filtered air (FA) on two separate occasions. Peripheral blood samples were collected and bronchoscopy with biopsy sampling and lavages was performed at 1.5h post exposures in group 1 (n=13), at 6h in group 2 (n=15) and at 18h in group 3 (n=15). Total and differential cell counts were assessed in blood, bronchial tissue and airway lavages.RESULTS: In peripheral blood, we observed fewer neutrophils 1.5h after ozone compared with the parallel air exposure (-1.1±1.0x10(9) cells/L, p<0.01), at 6h neutrophil numbers were increased compared to FA (+1.2±1.3x10(9) cells/L, p<0.01), and at 18h this response had fully attenuated. Ozone induced a peak in neutrophil numbers at 6h post exposure in all compartments examined, with a positive correlation between the response in blood and bronchial biopsies.CONCLUSIONS: These data demonstrate a systemic neutrophilia in healthy subjects following an acute ozone exposure, which mirrors the inflammatory response in the lung mucosa and lumen. This relationship suggests that blood neutrophilia could be used as a relatively simple functional biomarker for the effect of ozone on the lung.
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| 96279. |
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| 96280. |
- Bosson, Jenny, et al.
(author)
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Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy humans
- 2008
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 31:6, s. 1234-1240
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Journal article (peer-reviewed)abstract
- Exposure to particulate matter and ozone cause adverse airway reactions. Individual pollutant effects are often addressed separately, despite coexisting in ambient air. The present investigation was performed to study the effects of sequential exposures to diesel exhaust (DE) and ozone on airway inflammation in human subjects. Healthy subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial wash (BW) sampling on two occasions. Once following a DE exposure (with 300 mug.m(-3) particles with a 50% cut-off aerodynamic diameter of 10 mum) with subsequent exposure to O(3) (0.2 ppm) 5 h later. The other bronchoscopy was performed after a filtered air exposure followed by an ozone exposure, using an identical protocol. Bronchoscopy was performed 24 h after the start of the initial exposure. Significant increases in neutrophil and macrophage numbers were found in BW after DE followed by ozone exposure versus air followed by ozone exposure. DE pre-exposure also raised eosinophil protein X levels in BAL compared with air. The present study indicates additive effects of diesel exhaust on the ozone-induced airway inflammation. Together with similar results from a recent study with sequential diesel exhaust and ozone exposures, the present data stress a need to consider the interaction and cumulative effects of different air pollutants.
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