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


METHODS
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 microg b.d.) in a placebo-controlled double-blind study. BAL fluid and biopsies were processed to evaluate HLA-DR and hsp70 expression by immunochemistry methods.


RESULTS
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.


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 activity of APCs, which is essential for the initiation and modulation of the 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.
Bertorelli
G
G
Department of Respiratory Disease, University of Parma, Italy.
Bocchino
V
V
Zhuo
X
X
Chetta
A
A
Del Donno
M
M
Foresi
A
A
Testi
R
R
Olivieri
D
D
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy / Q000379:methods; D003713:Dendritic Cells / Q000378:metabolism; D004311:Double-Blind Method; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D000068298:Fluticasone; D006684:HLA-DR Antigens / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D006684:HLA-DR Antigens; D018840:HSP70 Heat-Shock Proteins; D000068298:Fluticasone