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 constitutive 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 only type I IL-1R. Genistein inhibited the 125I-labeled IL-1alpha binding to TIG-1 cells in both a time and dose dependent manner. Scatchard plot analysis 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 cycloheximide did not inhibit the down-regulatory effect of genistein. These results indicate that genistein inhibits IL-1RI expression, not at the transcriptional level, but at the post-translational level. IL-1RI expression, IL-1R associated kinase (IRAK) activity and IL-1-induced-IL-6 production were all down-regulated by pretreatment with genistein. These findings indicate that tyrosine kinase activity is essential for the constitutive expression of functional IL-1RI.