Berman B, Smith B
Department of Dermatology, University of California, Davis, School of Medicine.
Exp Cell Res. 1989 Jul;183(1):215-28. doi: 10.1016/0014-4827(89)90431-x.
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.
对胰蛋白酶具有特异性的丝氨酸蛋白酶抑制剂可抑制干扰素-γ（INF-γ）诱导的人杂交表皮细胞系（H12）、真皮成纤维细胞和原代角质形成细胞上HLA-DR的表达。对胰凝乳蛋白酶或木瓜蛋白酶具有特异性的蛋白酶抑制剂不能抑制INF-γ。胰蛋白酶抑制剂的抑制作用与糖皮质激素的抑制作用相似，因为它是一个短暂的事件，随着暴露于INF-γ时间的延长而减弱，并且通过添加来自产气荚膜梭菌的二丁酰环化AMP（dbcAMP）和磷脂酶C（PLC）可使其逆转。在H12细胞中，dbcAMP和PLC增强HLA-DR的INF-γ诱导，但在没有INF-γ的情况下不会诱导。有证据表明，蛋白酶抑制剂以及dbcAMP和PLC可能在翻译后位点以及INF-γ信号转导过程中调节HLA-DR的表达。这些结果表明，在暴露于INF-γ后，细胞HLA-DR抗原表达可能需要类胰蛋白酶活性。
