Tyrosine kinase inhibitors, genistein and herbimycin A, do not block interleukin-one β-induced activation of NF-κB in rat mesangial cells

We have previously demonstrated that interleukin-oneβ (IL-1β) rapidly induces tyrosine phosphorylation of several proteins in the renal mesangial cell. Two mechanistically distinct tyrosine kinase inhibitors, genistein and herbimycin A, block the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by IL-1β in rat mesangial cells. Since both COX-2 and iNOS promoters have a κB binding motif, we have evaluated the effects of tyrosine kinase inhibitors on IL-1β-induced nuclear factor-κB (NF-κB) activation by electromobility shift assays. IL-1β rapidly induced the translocation of NF-κB in rat mesangial cells. However, the tyrosine kinase inhibitors, genistein and herbimycin A, failed to block the translocation of NF-κB at concentrations which abolish COX-2 and iNOS mRNA expression. These data suggest that an upstream tyrosine kinase pathway may not be required for IL-1β-induced NF-κB activation and that the tyrosine kinase pathway may converge with the NF-κB pathway down-stream of NF-κB activation in rat mesangial cells.