Heat shock protein 70 upregulation is related to HLA‐DR expression in bronchial asthma. Effects of inhaled glucocorticoids

Abstract

Antigen processing determines the production of peptides from antigens — including allergens — and their binding to class II major histocompatibility complex molecules, that stimulate T-cell responses. Heat shock protein (hsp) 70 are recognized to have a role in chaperoning antigenic peptides and in facilitating class II peptide assembly. We studied the HLA-DR and hsp70 expression on BAL cells and bronchial biopsies from asthmatics, as well as the effect of low dose fluticasone propionate treatment. Twenty-three asthmatics and eight normal subjects were selected. In each subject BAL and bronchial biopsies were performed. Eighteen out of 23 asthmatics, underwent the second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate treatment (250 μg bd) in a placebo-controlled double-blind study. BAL fluid and biopsies were processed to evaluate HLA-DR and hsp70 expression by immunochemistry methods. Hsp70 and HLA-DR upregulation was present on professional and non-professional antigen presenting cells (APCs). In asthmatics, the hsp70 and HLA-DR expression was higher in BAL (hsp70 P < 0.001, HLA-DR P < 0.001) and bronchial epithelium (hsp70 P < 0.001, HLA-DR P < 0.001) when compared with controls. We also observed a significant correlation between hsp70 and HLA-DR expression in BAL (P < 0.005) and epithelium (P < 0.001). Fluticasone propionate treatment down-regulated the hsp70 and HLA-DR expression in BAL (hsp70 P < 0.001, HLA-DR P < 0.05) and bronchial epithelium (hsp70 P < 0.05, HLA-DR P < 0.05). A serial section comparison study showed that CD1a⁺ cells and macrophages were positive for both hsp70 and HLA-DR in the submucosa. Our results support the hypothesis that hsp70 over-expression implies a potential role for these proteins in antigen processing and/or presentation resulting in an increased activity of APCs, which is essential for the initiation and modulation of the asthmatic immune response in chronic asthma. Fluticasone propionate induces down-regulation of HLA-DR and hsp70 molecules thus regulating inflammation by affecting key mechanisms of the allergic response.