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dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant.

Brandelius, Angelica LU ; Yudina, Yulyana LU ; Calvén, Jenny LU ; Bjermer, Leif LU ; Andersson, Morgan LU ; Persson, Carl LU and Uller, Lena LU (2011) In Pulmonary Pharmacology & Therapeutics 24. p.59-66
Abstract
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)... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pulmonary Pharmacology & Therapeutics
volume
24
pages
59 - 66
publisher
Elsevier
external identifiers
  • WOS:000288300600008
  • PMID:20951221
  • Scopus:79251595016
ISSN
1522-9629
DOI
10.1016/j.pupt.2010.10.004
language
English
LU publication?
yes
id
3e8a1c49-b6ff-421c-aabf-bafc9a4aa7c8 (old id 1711079)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20951221?dopt=Abstract
date added to LUP
2010-11-08 09:09:29
date last changed
2016-11-13 04:27:57
@misc{3e8a1c49-b6ff-421c-aabf-bafc9a4aa7c8,
  abstract     = {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.},
  author       = {Brandelius, Angelica and Yudina, Yulyana and Calvén, Jenny and Bjermer, Leif and Andersson, Morgan and Persson, Carl and Uller, Lena},
  issn         = {1522-9629},
  language     = {eng},
  pages        = {59--66},
  publisher    = {ARRAY(0xb4f8328)},
  series       = {Pulmonary Pharmacology & Therapeutics},
  title        = {dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant.},
  url          = {http://dx.doi.org/10.1016/j.pupt.2010.10.004},
  volume       = {24},
  year         = {2011},
}