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Respiratory Research
Published in: Respiratory Research 1/2016

Open Access 01-12-2016 | Research

Th-17 regulatory cytokines inhibit corticosteroid induced airway structural cells apoptosis

Authors: Rabih Halwani, Asma Sultana, Roua Al-Kufaidy, Amer Jamhawi, Alejandro Vazquez-Tello, Saleh Al-Muhsen

Published in: Respiratory Research | Issue 1/2016

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Abstract

Background

Although corticosteroid is a powerful anti-inflammatory drug that is used widely to control asthma, still severe asthmatics can develop steroid resistance. Airway fibroblasts are quite resistant to steroids during Idiopathic pulmonary fibrosis (IPF) and fibrosis in asthmatic lungs is not always controlled. Th-17 regulatory cytokine which are elevated in lung tissues of asthmatics were shown to enhance the survival of various types of cells. STAT factors are central to this anti-apoptotic function. However, it is not yet clear whether these cytokines contribute to steroid hypo-responsiveness in asthma. Therefore, in this study, we investigated the ability of Th-17 regulatory cytokines, specifically IL-21, IL22 and IL23, to protect structural airway cells against dexamethasone-induced apoptosis.

Methods

Primary human fibroblasts, ASM cells, and lung endothelial cells line were treated with IL-21, IL-22, and IL-23 cytokines before incubation with dexamethasone and the level of apoptosis was determined by measuring cellular Annexin-V using Flow cytometry.

Results

Our data indicated that treatment with Th-17 regulatory cytokines was effective in inhibiting induced apoptosis for both fibroblasts and endothelial cells but not ASM cells. STAT3 phosphorylation levels were also upregulated in fibroblasts and endothelial upon treatment with these cytokines. Interestingly, inhibiting STAT3 phosphorylation abrogated IL-21, IL-22, and IL-23 anti-apoptotic effect on fibroblasts and endothelial cells.

Conclusions

This data suggest that Th-17 regulatory cytokines may play a critical role in regulating the survival of fibroblasts during asthma, IPF as well as other chronic lung inflammatory diseases leading to enhanced fibrosis. Accordingly, findings of this paper may pave the way for more extensive research on the role of these regulatory cytokines in fibrosis development in various chronic inflammatory diseases.
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Metadata
Title
Th-17 regulatory cytokines inhibit corticosteroid induced airway structural cells apoptosis
Authors
Rabih Halwani
Asma Sultana
Roua Al-Kufaidy
Amer Jamhawi
Alejandro Vazquez-Tello
Saleh Al-Muhsen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2016
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-015-0307-2

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