Bronchial thermoplasty may increase steroid sensitivity by upregulating the expression of the glucocorticoid receptor

Abstract

Background: Bronchial thermoplasty is applied to patients with severe asthma. Besides reducing airway wall remodeling and increasing quality of life, it was reported that the use of steroid could be reduced. We reported earlier that glucocorticoid receptor (GR) regulating heat shock proteins were affected by bronchial thermoplasty. Aim:In vitro assessment regarding the effect of heat on the expression of the GR by airway smooth muscle cells (ASMC) and epithelial cells (EC). Methods: Immortalized human bronchial epithelium (BEAS-2B), human primary EC (n=14) and ASMC (n=27) were treated with increasing temperatures (37, 45, 55, 65oC) for 10 seconds. The cells were incubated for 24h and 48h, in the presence and absence of steroids (10-8M). GR expression was determined by qPCR, Western-blotting and immunohistochemistry. Results: ASMC were significantly more sensitive to heat than EC. ASMC and BEAS-2B cells showed signs of apoptosis at temperatures above 50oC, while primary EC showed no sign of cell death. Exposure to 65oC reduced the expression of the GR in ASMC without any significant difference between controls, asthma, and COPD patients at 24h or 48h. In contrast, increasing heat significantly upregulated the expression of the GR in EC, but not in BEAS-2B cells. The cell type specific response of the GR to heat was confirmed on the level of transcription, and protein expression. Conclusion: Bronchial thermoplasty or heat application modifies the expression of the GR in a cell type specific manner. This may explain the reduced requirement of steroids for asthma therapy after bronchial thermoplasty.