| dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant. | |
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MedLine Citation:
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PMID: 20951221 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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RATIONALE: Thymic Stromal Lymphopoietin (TSLP) is considered a hub cytokine that activates dendritic cells and T-cells producing asthma-like Th(2)-inflammation. Viral stimuli, a major cause of asthma exacerbations, have been shown to induce overexpression of TSLP in asthmatic epithelium. Capsazepine has multiple effects and is of interest because it relaxes human small airways. Here we have explored effects of capsazepine on viral surrogate (dsRNA)-induced TSLP and other cytokines (TNF-alpha, IL-8) in human bronchial epithelial cells (HBEC) from healthy and asthmatic donors. METHODS: HBEC obtained from healthy and asthmatic subjects were grown and stimulated with dsRNA. Cells pre-treated with capsazepine (3-30μM), dexamethasone (0.1-10μM) or an IkappaB-kinase inhibitor (PS1145, 30μM) were also exposed to dsRNA (10μg/ml). Cells and supernatants were harvested for analyses of gene expression (RT-qPCR) and protein production (ELISA,Western blot). RESULTS: dsRNA-induced TSLP, TNF-alpha, and IL-8 in asthmatic and non-asthmatic HBEC. Dexamethasone attenuated gene expression and protein release whereas capsazepine dose-dependently, and similar to a non-relaxant NFkB inhibitor (PS1145), completely inhibited dsRNA-induced TSLP and TNF-alpha in both healthy and asthmatic HBEC. Capsazepine reduced dsRNA-induced IL-8 and it prevented dsRNA-induced loss of the NF-κB repressor protein IkBα. CONCLUSION: Additional to its human small airway relaxant effects we now demonstrate that capsazepine has potent anti-inflammatory effects on viral stimulus-induced cytokines in HBEC from healthy as well as asthmatic donors. Based on these data we suggest that exploration of structure-activity amongst the multifaceted capsazepinoids is warranted in search for compounds of therapeutic value in viral-induced, steroid-resistant asthma. |
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Authors:
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Angelica Brandelius; Yulyana Yudina; Jenny Calvén; Leif Bjermer; Morgan Andersson; Carl Persson; Lena Uller |
Publication Detail:
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Type: Journal Article Date: 2010-10-14 |
Journal Detail:
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Title: Pulmonary pharmacology & therapeutics Volume: 24 ISSN: 1522-9629 ISO Abbreviation: Pulm Pharmacol Ther Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9715279 Medline TA: Pulm Pharmacol Ther Country: England |
Other Details:
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Languages: eng Pagination: 59-66 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Unit of Respiratory Immunopharmacology, Department of Experimental Medical Science, BMC D12, Lund University, 221 84 Lund, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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