Differential effects of protein tyrosine kinase inhibitors on interferon-gamma-induction of major histocompatibility complex class II and intercellular adhesion molecule-1 expression in human corneal epithelial cells

Purpose: Interferon (IFN)-gamma induces major histocompatibility complex (M HC) class II and intercellular adhesion molecule-1 (ICAM-1) expression on h uman corneal epithelial (HCE) cells. So far, it has not been clarified whet her both inductions by IFN-gamma use the same signal transduction pathway. Therefore, in the present study, we tried to determine the significance of the protein tyrosine kinase (PTK)-dependent signaling pathway in the induct ion of both MHC class II and ICAM-1 expression by IFN-gamma in cultured HCE cells. Methods: Cultured HCE cells were treated with human recombinant IFN-gamma. The induction of protein tyrosine phosphorylation of proteins including PTK s, janus kinase (JAK)1, and JAK2, was examined by Western blotting and immu noprecipitation. The effects of treatment of HCE cells with specific PTK in hibitors on IFN-gamma -induction of MHC class II and ICAM-1 expression were examined by flow cytometry. Results: IFN 1 (Interferon) induced tyrosine phosphorylation of multiple su bstrates, particularly that of 75,000; 90,000; 130,000; and 160,000 molecul ar weight proteins including JAK1 and JAK2 in cultured HCE cells. The PTK i nhibitors, herbimycin A and genistein, inhibited tyrosine phosphorylation o f those proteins. Also, these PTK inhibitors prevented IFN-gamma induction of MHC class II synthesis and surface expression. However, neither herbimyc in A nor genistein had any effect on IFN-gamma -induction of ICAM-1 express ion. Conclusions: Tyrosine phosphorylation of proteins including JAK1 and JAK2 i s essential for IFN-gamma -induction of MHC class II expression, but not cr itical for that of ICAM-1 expression in cultured HCE cells. In addition, it is suggested that the IFN-gamma -induction of MHC class II requires PTK ac tivities not only in the primary JAK-signal transducers and activators of t ranscription (STAT) pathway but also in the subsequent pathway mediated by IFN-gamma -induced intermediate proteins. Jpn J Ophthalmol 2001;45:13-21 (C ) 2001 Japanese Ophthalmological Society.