Induction of interleukin-12/p40 by superantigens in macrophages is mediated by activation of nuclear factor-kappaB

Cell Immunol. 2000 Jan 10;199(1):50-7. doi: 10.1006/cimm.1999.1595.

Abstract

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 kappaB (NF-kappaB). The NF-kappaB heterodimer bound to the NF-kappaB 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-kappaB. 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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA / genetics
  • DNA / metabolism
  • Genes, MHC Class II / genetics
  • Genes, MHC Class II / immunology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / chemistry
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Ligands
  • Lipopolysaccharides / immunology
  • Macrophages / enzymology
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / chemistry
  • NF-kappa B / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Receptor Aggregation
  • Signal Transduction
  • Superantigens / immunology*
  • Up-Regulation

Substances

  • Histocompatibility Antigens Class II
  • Ligands
  • Lipopolysaccharides
  • NF-kappa B
  • Superantigens
  • Interleukin-12
  • DNA
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C