Trypsin inhibitors inhibit induction by interferon-gamma of HLA-DR antigen expression on human skin cells.
Serine protease inhibitors with a specificity for trypsin inhibit interferon-gamma (INF-gamma)-induced HLA-DR expression on a hybrid human epidermal cell line (H12), dermal fibroblasts, and primary keratinocytes. Protease inhibitors with a specificity for chymotrypsin or papain fail to inhibit IFN-gamma. The inhibitory effect of the trypsin inhibitors is similar to that of glucocorticoids in that it is a transient event, fading with length of exposure to IFN-gamma, and is reversed by the addition of dibutyryl cyclic AMP (dbcAMP) and phospholipase C(PLC) from Clostridium perfringens. In H12 cells, dbcAMP and PLC enhance the IFN-gamma induction of HLA-DR, but do not induce in the absence of INF-gamma. Evidence suggests that the protease inhibitors, as well as dbcAMP and PLC, may modulate HLA-DR expression at a post-translational site as well as during IFN-gamma signal transduction. These results suggest that trypsin-like protease activity may be required for cellular HLA-DR antigen expression following exposure to IFN-gamma.
Berman
B
B
Department of Dermatology, University of California, Davis, School of Medicine.
Smith
B
B
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007633:Keratins; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000502:physiology; D011971:Receptors, Immunologic / Q000378:metabolism; D017471:Receptors, Interferon; D013997:Time Factors; D014221:Triamcinolone / Q000031:analogs & derivatives / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D006684:HLA-DR Antigens; D011480:Protease Inhibitors; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D014361:Trypsin Inhibitors; D014221:Triamcinolone; C012716:amcinonide; D003994:Bucladesine; D007633:Keratins; D007371:Interferon-gamma; D010738:Type C Phospholipases