TYROSINE KINASE-ACTIVITY IS INVOLVED IN THE PROTEIN-KINASE-C INDUCED EXPRESSION OF INTERLEUKIN-1-BETA GENE IN MONOCYTIC CELLS

The role of protein tyrosine kinases in the expression of interleukin-1beta (IL-1beta) gene in response to phorbol esters (PMA) in THP-1 cell line was investigated. Genistein, a specific tyrosine kinase inhibitor, inhibited PMA induced IL-1beta protein and mRNA levels in THP-1 cells. Genistein did not have a significant effect on PMA induced activity in transient transfection assays using reporter gene constructs containing the PMA responsive sequence of the IL-1beta gene linked to IL-1beta promoter, or five repeats of PMA responsive sites (AP-1 sites) in front of a thymidine kinase promoter. This indicates that the tyrosine kinase activity required for the PMA induced IL-1beta expression is coupled downstream from or functions independent of the PMA induced AP-1 activity.