Induction of glucocorticoid receptor-β expression in epithelial cells of asthmatic airways by T-helper type 17 cytokines

• Published in: Clinical and experimental allergy 2010-09, Vol.40 (9), p.1312-1322
• Main Authors: Vazquez-Tello, A., Semlali, A., Chakir, J., Martin, J. G., Leung, D. Y., Eidelman, D. H., Hamid, Q.
• Format: Article
• Language: English
• Subjects: Adult; Asthma - immunology; Biological and medical sciences; Bronchi - immunology; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; dexamethasone; Dexamethasone - pharmacology; Epithelial Cells - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; glucocorticoid receptor; Humans; IL-17A; IL-17F; Interleukin-17 - immunology; Interleukin-17 - metabolism; Male; Medical sciences; mild asthma; Pneumology; primary airway epithelial cells; Receptors, Glucocorticoid - metabolism; steroid insensitivity; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Helper-Inducer - immunology; Th17 cells; Up-Regulation - drug effects
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2010.03544.x

Summary 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.