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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Induction of glucocorticoid receptor-β expression in epithelial cells of asthmatic airways by T-helper type 17 cytokines
Clinical and Experimental Allergy, Volume 40, No. 9, Year 2010
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Description
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 (P≤0.05). 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 (P≤0.05). 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. © 2010 Blackwell Publishing Ltd.
Authors & Co-Authors
Vazquez-Tello, A.
Canada, Montreal
Meakins-christie Laboratories
Saudi Arabia, Riyadh
College of Medicine
Semlali, Abdelhabib
Canada, Quebec
Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval
Chakir, Jamila
Canada, Quebec
Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval
Martin, James G.
Canada, Montreal
Meakins-christie Laboratories
Canada, Montreal
Centre Universitaire de Santé Mcgill
Leung, D. Y.
United States, Denver
National Jewish Health
Eidelman, D. H.
Canada, Montreal
Meakins-christie Laboratories
Canada, Montreal
Centre Universitaire de Santé Mcgill
Hamid, Qùtayba A.
Canada, Montreal
Meakins-christie Laboratories
Canada, Montreal
Centre Universitaire de Santé Mcgill
Statistics
Citations: 120
Authors: 7
Affiliations: 5
Identifiers
Doi:
10.1111/j.1365-2222.2010.03544.x
ISSN:
09547894
e-ISSN:
13652222