The mechanism by which interleukin-1α (IL-1α) activates NF-κB DNA-binding activity is not completely understood. While it is well established that protein kinase C can activate NF-κB, neither protein kinase C nor protein kinase A appears to be critical in the induction of NF-κB by IL-1α. Since a number of growth factors signal via protein tyrosine kinase, in this study we examined a possible involvement of protein tyrosine kinase in the IL-1α-induced NF-κB. The results showed that in the murine pre-B cell line 7OZ/3 and in the murine T cell line EL-4 6.1 C10 IL-1α-induced NF-κB was associated with transient increase in protein tyrosine kinase activity. Pre-treatment of these cell lines with herbimycin A, an inhibitor of tyrosine kinase activity, blocked the IL-1α-enhanced protein tyrosine kinase activity and the IL-1α-induced NF-κB DNA-binding activity. Herbimycin A at concentrations sufficient to block IL-1α-induced NF-κB did not block the phorbol 12-myristate 13-acetate(PMA)-induced NF-κB. The data suggest that IL-1α and PMA activate NF-κB by different pathways and that induction of NF-κB DNA-binding activity by IL-1 might be dependent on protein tyrosine phosphorylation.
