Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes.

It is not known whether one or both of the interleukin 1 (IL1) receptors mediates the induction of the DNAbinding protein NF-KB.Nuclear extracts of the murine lines EL4.NOB.1 and 70213, which bear the type I (80 kDa) and type I1 (67 kDa) IL1 receptor, respectively, were analyzed by an electrophoretic mobility shift assay.A 265-base pair sequence of the human serum amyloid A gene or a synthetic oligonucleotide each containing the NF-KB site were used as the DNA probes.IL1 induction of NF-KB was rapid (optimal at 15-30 min) and transient in both cell types.The IL1 receptor antagonist (ILlra), which binds strongly to the type I receptor, inhibited the NF-KB response in both cell lines.ILlra did not bind to the type I1 receptor on 70213 cells as judged by competition for binding with ''61-ILla.When 1261-ILlra binding to 702/3 cells was measured, a small number (10/cell) of high affinity sites (& = 6 % 10"' M) were detected.These were likely to have been type I receptor because an antibody to this inhibited the NF-KB induction in 70213 cells (as well as EL4).Potential signal transduction mechanisms involving protein kinase C or oxygen radicals were studied.Phorbol 12-myristate 13-acetate induced NF-KB with a similar time course to IL1 in 70213 but only after 4 h in EL4.IL1 was unaffected by a protein kinase C inhibitor (staurosporine).HzOz did not mimic IL1, and IL1 was not inhibited by an antioxidant.The type I receptor mediates the induction of NF-KB in response to IL1 via a signaling mechanism that still remains to be identified.The central role of IL1' in mediating multiple immunological and inflammatory events has been documented extensively (Dinarello, 1991).IL1 binds independently to two dis-