IL-10 promotes survival of microglia without activating Akt

J Neuroimmunol. 2002 Jan;122(1-2):9-19. doi: 10.1016/s0165-5728(01)00444-1.

Abstract

IL-10 is an anti-inflammatory cytokine that has recently been shown to promote survival of neurons and glia. Here we establish that IL-10 induces phosphorylation of Stat3 on Tyr(705) and serves as a survival factor for N13 microglial cells. Recombinant IL-10 (10 ng/ml) decreases growth factor withdrawal-induced apoptosis by 50%, as assessed by TUNEL. In contrast to IL-10, IGF-I increases enzymatic activity of PI 3-kinase and causes phosphorylation on serine(473) of Akt but does not prevent microglial apoptosis. These data establish that IL-10 activates Stat3 and inhibits the mitochondrial pathway of cell death without activating the Akt cell survival pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Division
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coloring Agents
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation / drug effects
  • Insulin-Like Growth Factor I / pharmacology
  • Interleukin-10 / pharmacology*
  • Mice
  • Microglia / cytology*
  • Microglia / drug effects
  • Microglia / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptor, IGF Type 1 / biosynthesis
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin-10
  • STAT3 Transcription Factor
  • Serine / metabolism
  • Tetrazolium Salts
  • Thiazoles
  • Trans-Activators / metabolism
  • Tyrosine / metabolism

Substances

  • Coloring Agents
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tetrazolium Salts
  • Thiazoles
  • Trans-Activators
  • Interleukin-10
  • Tyrosine
  • Serine
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • thiazolyl blue