Tyrosine kinase is essential for the constitutive expression of type I interleukin-1 receptor in human fibroblast cells

The effect of genistein, an inhibitor of tyrosine kinase, on the constituti ve expression of type I interleukin-1 receptor (IL-1RI) was examined in the human lung fibroblast cell line TIG-1, which has been shown to express onl y type I IL-1R, Genistein inhibited the I-125-labeled IL-1 alpha binding to TIG-1 cells in both a time and dose dependent manner. Scatchard plot analy sis revealed that the number of IL-1RI decreased with no change in binding affinity. Genistein did not affect the level of IL-1RI mRNA, and cyclohexim ide did not inhibit the down-regulatory effect of genistein, These results indicate that genistein inhibits IL-1RI expression, not at the trascription al level, but at the post-translational level. IL-1RI expression, IL-1R ass ociated kinase (IRAK) activity and IL-1-induced-IL-6 production mere all do wn-regulated by pretreatment with genistein, These findings indicate that t yrosine kinase activity is essential for the constitutive expression of fun ctional IL-1RI.