Induction of Interleukin-12/p40 by Superantigens in Macrophages Is Mediated by Activation of Nuclear Factor-κB

Multimerization of the MHC class II molecule by superantigens results in activation of cellular signal transduction pathways in macrophage and B cells. Here we show that superantigen staphylococcal enterotoxin B (SEB) induces IL-12/p40 secretion in macrophages. SEB-induced expression of the IL-12/p40 gene involves activation and nuclear translocation of nuclear factor κB (NF-κB). The NF-κB heterodimer bound to the NF-κB consensus sequence of the IL-12/p40 gene promoter is p50/C-Rel. Inhibition of PKC and PKA activation results in suppression of activation and translocation of NF-κB. We conclude that signals for IL-12/p40 gene transcription from MHC class II molecules follow activation of PKC and PKA, which in turn leads to the activation and translocation of NF-κB to the nucleus. Our study suggests that superantigens are capable of influencing the nature of the immune response by regulating cytokine production. Induction of IL-12 production by superantigens may therefore play a role in the regulation of Th 1-mediated immune response and autoimmune disease.