Journal
CLINICAL AND EXPERIMENTAL ALLERGY
Volume 40, Issue 9, Pages 1312-1322Publisher
WILEY
DOI: 10.1111/j.1365-2222.2010.03544.x
Keywords
dexamethasone; glucocorticoid receptor; IL-17A; IL-17F; mild asthma; primary airway epithelial cells; steroid insensitivity; Th17 cells
Categories
Funding
- Richard and Edith Strauss Foundation (Montreal, QC, Canada)
- Canadian Institutes of Health Research (Ottawa, ON, Canada)
- J. T. Costello Memorial Research Fund (Montreal, QC, Canada)
- NIAID [1R01AI070140]
Ask authors/readers for more resources
Background Corticosteroid insensitivity in asthmatics is associated with an increased expression of glucocorticoid receptor-beta (GR-beta) 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-beta in bronchial epithelial cells. Objectives To confirm the expression of the GR-beta 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-beta in bronchial epithelial cells obtained from normal subjects and asthmatic patients. Methods The expression of IL-17A and F, GR-alpha and GR-beta was analysed in bronchial biopsies from mild asthmatics and normal subjects by Q-RT-PCR. Immunohistochemistry for IL-17 and GR-beta 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-RTPCR 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-alpha expression was significantly lower in the biopsies from asthmatics compared with controls. The expression of IL-17F and GR-beta 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-beta 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-beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available