Induction of glucocorticoid receptor‐β expression in epithelial cells of asthmatic airways by T‐helper type 17 cytokines |
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| Authors: | A. Vazquez‐Tello A. Semlali J. Chakir J. G. Martin D. Y. Leung D. H. Eidelman Q. Hamid |
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| Affiliation: | 1. Meakins‐Christie Laboratories, Department of Medicine, Respiratory Division, McGill University, Montreal, QC, Canada;2. Asthma Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia;3. Centre de recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Sainte‐Foy, PQ, Canada;4. Research Institute of the McGill University Health Centre, Montreal, QC, Canada;5. Department of Pediatrics, National Jewish Health, Denver, CO, USA |
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| Abstract: | Background Corticosteroid insensitivity in asthmatics is associated with an increased expression of glucocorticoid receptor‐β (GR‐β) in many cell types. T‐helper type 17 (Th17) cytokine (IL‐17A and F) expressions increase in mild and in difficult‐to‐treat asthma. We hypothesize that IL‐17A and F cytokines alone or in combination, induce the expression of GR‐β in bronchial epithelial cells. Objectives To confirm the expression of the GR‐β and IL‐17 cytokines in the airways of normal subjects and mild asthmatics and to examine the effect of cytokines IL‐17A and F on the expression of GR‐β in bronchial epithelial cells obtained from normal subjects and asthmatic patients. Methods The expression of IL‐17A and F, GR‐α and GR‐β was analysed in bronchial biopsies from mild asthmatics and normal subjects by Q‐RT‐PCR. Immunohistochemistry for IL‐17 and GR‐β was performed in bronchial biopsies from normal and asthmatic subjects. The expression of IL‐6 in response to IL‐17A and F and dexamethasone was determined by Q‐RT‐PCR using primary airway epithelial cells from normal and asthmatic subjects. Results We detected significantly higher levels of IL‐17A mRNA expression in the bronchial biopsies from mild asthmatics, compared with normal. GR‐α expression was significantly lower in the biopsies from asthmatics compared with controls. The expression of IL‐17F and GR‐β in biopsies from asthmatics was not significantly different from that of controls. Using primary epithelial cells isolated from normal subjects and asthmatics, we found an increased expression of GR‐β in response to IL‐17A and F in the cells from asthmatics (P0.05). This effect was only partially significant in the normal cells. Dexamethasone significantly decreased the IL‐17‐induced IL‐6 expression in cells from normal individuals but not in those from asthmatics (P0.05). Conclusion Evidence of an increased GR‐β expression in epithelial cells following IL‐17 stimulation suggests a possible role for Th17‐associated cytokines in the mechanism of steroid hypo‐responsiveness in asthmatic subjects. Cite this as: A. Vazquez‐Tello, A. Semlali, J. Chakir, J. G. Martin, D. Y. Leung, D. H. Eidelman and Q. Hamid, Clinical & Experimental Allergy, 2010 (40) 1312–1322. |
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| Keywords: | dexamethasone glucocorticoid receptor IL‐17A IL‐17F mild asthma primary airway epithelial cells steroid insensitivity Th17 cells |
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