The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription

Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8686-91. doi: 10.1073/pnas.0500419102. Epub 2005 Jun 3.


The antiinflammatory cytokine IL-10 inhibits the production of multiple, diverse inflammatory mediators from activated macrophages and dendritic cells, a process requiring STAT3 activation. However, the mechanisms involved in the broad inhibitory effects of IL-10 are controversial. I eliminated the contribution of the major confounding variable to understanding the antiinflammatory response, the 3' UTR region of inflammatory mediator genes, through knock-in mutation and analysis of the effects of IL-10 on transcription rate of inflammatory genes. IL-10 activates STAT3 to act indirectly by selectively inhibiting gene transcription independent of general effects on NF-kappaB or posttranscriptional mRNA processing through a process that reduces the overall transcriptional rate of specific genes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • I-kappa B Proteins
  • Immunoblotting
  • Inflammation Mediators / metabolism*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor
  • Signal Transduction / physiology*
  • Trans-Activators / metabolism*


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Inflammation Mediators
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Interleukin-10