HEAT-SHOCK-PROTEIN-70 UP-REGULATION IS RELATED TO HLA-DR EXPRESSION IN BRONCHIAL-ASTHMA - EFFECTS OF INHALED GLUCOCORTICOIDS

Background and objective 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 pe ptide assembly. We studied the HLA-DR and hsp70 expression on BAL cell s and bronchial biopsies from asthmatics, as well as the effect of low dose fluticasone propionate treatment. Methods Twenty-three asthmatic s and eight normal subjects were selected. In each subject BAL and bro nchial biopsies were performed. Eighteen out of 23 asthmatics, underwe nt the second bronchoscopy after 6 weeks of low dose inhaled fluticaso ne propionate treatment (250 mu g bd) in a placebo-controlled double-b lind study. BAL fluid and biopsies were processed to evaluate HLA-DR a nd hsp70 expression by immunochemistry methods. Results Hsp70 and HLA- DR upregulation was present on professional and non-professional antig en presenting cells (APCs). In asthmatics, the hsp70 and KLA-DR expres sion was higher in BAL (hsp70 P<0.001, HLA-DR P<0.001) and bronchial e pithelium (hsp70 P<0.001, HLA-DR P<0.001) when compared with controls. We also observed a significant correlation between hsp70 and KLA-DR e xpression in BAL (P<0.005) and epithelium (P<0.001). Fluticasone propi onate 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. Conclusions 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 activ ity of APCs, which is essential for the initiation and modulation of t he asthmatic immune response in chronic asthma. Fluticasone propionate induces downregulation of HLA-DR and hsp70 molecules thus regulating inflammation by affecting key mechanisms of the allergic response.