HERBIMYCIN-A BLOCKS IL-1-INDUCED NF-KAPPA-B DNA-BINDING ACTIVITY IN LYMPHOID-CELL LINES

The mechanism by which interleukin-1-alpha (IL-1-alpha) activates NF-kappa-B DNA-binding activity is not completely understood. While it is well established that protein kinase C can activate NF-kappa-B, neither protein kinase C nor protein kinase A appears to be critical in the induction of NF-kappa-B by IL-1-alpha. 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-1-alpha-induced NF-kappa-B. The results showed that in the murine pre-B cell line 70Z/3 and in the murine T cell line EL-4 6.1 C10 IL-1-alpha-induced NF-kappa-B 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-1-alpha enhanced protein tyrosine kinase activity and the IL-1-alpha-induced NF-kappa-B DNA-binding activity. Herbimycin A at concentrations sufficient to block IL-1-alpha-induced NF-kappa-B did not block the phorbol 12-myristate 13-acetate (PMA)-induced NF-kappa-B. The data suggest that IL-1-alpha and PMA activate NF-kappa-B by different pathways and that induction of NF-kappa-B DNA-binding activity by IL-1 might be dependent on protein tyrosine phosphorylation.