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

Authors

  • A. Vazquez-Tello,

    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
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  • A. Semlali,

    1. Centre de recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Sainte-Foy, PQ, Canada
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  • J. Chakir,

    1. Centre de recherche de l'Institut de Cardiologie et de Pneumologie de Québec, Sainte-Foy, PQ, Canada
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  • J. G. Martin,

    1. Meakins-Christie Laboratories, Department of Medicine, Respiratory Division, McGill University, Montreal, QC, Canada
    2. Research Institute of the McGill University Health Centre, Montreal, QC, Canada
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  • D. Y. Leung,

    1. Department of Pediatrics, National Jewish Health, Denver, CO, USA
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  • D. H. Eidelman,

    1. Meakins-Christie Laboratories, Department of Medicine, Respiratory Division, McGill University, Montreal, QC, Canada
    2. Research Institute of the McGill University Health Centre, Montreal, QC, Canada
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  • Q. Hamid

    1. Meakins-Christie Laboratories, Department of Medicine, Respiratory Division, McGill University, Montreal, QC, Canada
    2. Research Institute of the McGill University Health Centre, Montreal, QC, Canada
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Correspondence:
Dr Qutayba Hamid, Meakins-Christie Laboratories, Department of Medicine, Respiratory Division, McGill University, 3626 St. Urbain Street, Montreal, QC, Canada H2X 2P2.
E-mail: qutayba.hamid@mcgill.ca

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 (Pleqslant R: less-than-or-eq, slant0.05). 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 (Pleqslant R: less-than-or-eq, slant0.05).

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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