Characterization of a glucocorticosteroid-induced inhibitor of interferon-gamma induction of HLA-DR expression.
Interferon gamma (IFN-gamma) induces human leukocyte antigen (HLA)-DR antigen expression on a variety of cell types, and in human skin cells this induction is inhibited by trypsin inhibitors. Recently a trypsin-like protease was characterized whose activity is required for HLA-DR induction in a hybrid epidermal cell line. Glucocorticosteroids also inhibit IFN-gamma-induced HLA-DR expression, and similarities have been noted between the inhibition by trypsin inhibitors and by glucocorticosteroids. To assess the possibility that glucocorticosteroid inhibition of IFN-gamma-induced HLA-DR expression might be due to induction of an inhibitor of trypsin activity that is re-expression, we examined culture medium supernates (CM) of glucocorticosteroid-treated cells for HLA-DR- and trypsin-inhibitory activities. We report here that CM of glucocorticosteroid-treated H12 cells contain inhibitors of HLA-DR expression and of trypsin activity, but that the two inhibitors are not identical. H12 cells constitutively secrete a greater than 30,000 MW, acid- and heat-stable trypsin inhibitor, whose expression is not modulated by glucocorticosteroid or IFN-gamma, and that does not inhibit IFN-gamma-induced HLA-DR expression. The HLA-DR inhibitor, on the other hand, is present only in CM of glucocorticosteroid-treated cells, is distinct from glucocorticosteroid itself, of a MW less than 500 and does not inhibit trypsin. We conclude, therefore, that the glucocorticosteroid inhibition of IFN-gamma-induced HLA-DR expression is by a mechanism other than secretion of a trypsin inhibitor.
Smith
B
B
Department of Dermatology, University of California, Davis School of Medicine.
Berman
B
B
D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D005938:Glucocorticoids; D006684:HLA-DR Antigens; D007369:Interferon Inducers; D014361:Trypsin Inhibitors; D007371:Interferon-gamma; D014568:Urokinase-Type Plasminogen Activator