Inhibition of Inflammatory Gene Transcription by IL-10 Is Associated with Rapid Suppression of Lipopolysaccharide-Induced Enhancer Activation

J Immunol. 2017 Apr 1;198(7):2906-2915. doi: 10.4049/jimmunol.1601781. Epub 2017 Feb 17.


IL-10 limits the magnitude of inflammatory gene expression following microbial stimuli and is essential to prevent inflammatory disease; however, the molecular basis for IL-10-mediated inhibition remains elusive. Using a genome-wide approach, we demonstrate that inhibition of transcription is the primary mechanism for IL-10-mediated suppression in LPS-stimulated macrophages and that inhibited genes can be divided into two clusters. Genes in the first cluster are inhibited only if IL-10 is included early in the course of LPS stimulation and is strongly enriched for IFN-inducible genes. Genes in the second cluster can be rapidly suppressed by IL-10 even after transcription is initiated, and this is associated with suppression of LPS-induced enhancer activation. Interestingly, the ability of IL-10 to rapidly suppress active transcription exhibits a delay following LPS stimulation. Thus, a key pathway for IL-10-mediated suppression involves rapid inhibition of enhancer function during the secondary phase of the response to LPS.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Chromatin Immunoprecipitation
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / immunology*
  • Inflammation / genetics*
  • Inflammation / immunology*
  • Interleukin-10 / immunology*
  • Lipopolysaccharides / immunology
  • Mice
  • Mice, Knockout
  • Polymerase Chain Reaction
  • Transcription, Genetic / immunology*


  • Lipopolysaccharides
  • Interleukin-10