Human microglial cells express a functional IL-12 receptor and produce IL-12 following IL-12 stimulation

Eur J Immunol. 2001 Nov;31(11):3228-39. doi: 10.1002/1521-4141(200111)31:11<3228::aid-immu3228>3.0.co;2-7.

Abstract

Microglial cells (MC) are IL-12 producers in the central nervous system. Here, we found that IL-12 receptor subunits beta1 and beta2 were both constitutively expressed, and up-regulated by IFN-gamma, in human primary MC. IL-12p70, after binding to its receptor, is internalized into vesicles that qualify as early endosomes as indicated by intracellular colocalization with transferrin. IL-12 induced tyrosine phosphorylation and nuclear translocation of STAT4. IL-12 signaling in human MC also involved members of the NFkappaB family. IL-12p70 and, more effectively, the combination of IL-12p70 and IFN-gamma, induced IL-12p40 mRNA expression and bioactive IL-12p70 production. Human MC, thus, express a functional IL-12 receptor and produce bioactive IL-12 following IL-12 stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Endosomes / metabolism
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / pharmacology*
  • Microglia / drug effects*
  • Microglia / metabolism
  • NF-kappa B / physiology
  • Phosphorylation
  • Protein Subunits
  • RNA, Messenger / analysis
  • Receptors, Interleukin / analysis*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • Trans-Activators / metabolism
  • Tyrosine / metabolism

Substances

  • DNA-Binding Proteins
  • IL12RB1 protein, human
  • IL12RB2 protein, human
  • NF-kappa B
  • Protein Subunits
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • Trans-Activators
  • Interleukin-12
  • Tyrosine
  • Interferon-gamma