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Open Access Research

Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils

Saleh Al-Muhsen1, Severine Letuve2, Alejandro Vazquez-Tello1, Mary Angeline Pureza1, Hamdan Al-Jahdali13, Ahmed S Bahammam4, Qutayba Hamid5 and Rabih Halwani1*

Author Affiliations

1 Asthma Research Chair and Prince Naif Center for Immunology Research, Department of Paediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia

2 Institut National de la Santé et de la Recherche Médicale (Inserm) U700 and Université Paris 7, Faculté de Médecine Denis Diderot, Site Bichat, Paris, France

3 King Saud University for health sciences, Riyadh, Saudi Arabia

4 Pulmonary Medicine Department, University Sleep Disorders Center, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia

5 Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada

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Respiratory Research 2013, 14:34  doi:10.1186/1465-9921-14-34

Published: 13 March 2013

Abstract

Background

Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood.

Objective

In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines.

Methods

Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays.

Results

The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release.

Conclusions

Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.

Keywords:
Asthma; Eosinophils; Th17 cytokines; Pro-fibrotic cytokines; TGF-β; IL-11