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The role of protein tyrosine kinases in the expression of interleukin-1 beta (IL-1 beta) gene in response to phorbol esters (PMA) in THP-1 cell line was investigated. Genistein, a specific tyrosine kinase inhibitor, inhibited PMA induced IL-1 beta 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-1 beta gene linked to IL-1 beta 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-1 beta expression is coupled downstream from or functions independent of the PMA induced AP-1 activity.
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Palkama et al. (1993) studied this question.
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