IL-10-mediated suppression of TNF-alpha production is independent of its ability to inhibit NF kappa B activity

Eur J Immunol. 1998 May;28(5):1719-26. doi: 10.1002/(SICI)1521-4141(199805)28:05<1719::AID-IMMU1719>3.0.CO;2-Q.

Abstract

IL-10 has a well-characterized anti-inflammatory role that includes the suppression of inflammatory cytokine (e.g. TNF-alpha) production by monocytic/macrophage cells. Both transcriptional and post-transcriptional/translational mechanisms have been proposed to explain this process. In this study we observed that IL-10 inhibited nuclear NF kappa B DNA binding activity without affecting I kappa B degradation or translocation of NF kappa B subunits to the nucleus. While the suppression of NF kappa B in 70Z/3 pre-B cells correlated with suppression of NF kappa B transcriptional activity and expression of surface IgM, it did not correlate with the production of TNF-alpha mRNA or protein in RAW 264.7 macrophages. Similar observations in the macrophages were made with a second anti-inflammatory cytokine, IL-4. Therefore we conclude that although IL-10 or IL-4 can suppress NF kappa B activity, this appears to have little effect on the expression of the TNF-alpha gene and is unlikely to be the basis of the anti-inflammatory effects of these cytokines.

MeSH terms

  • Animals
  • Biological Transport
  • Cell Line
  • Cell Nucleus / metabolism
  • DNA / immunology
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • I-kappa B Proteins*
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-10 / physiology*
  • Interleukin-4 / physiology
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / metabolism
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Protein Binding / immunology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Transcription Factor RelA
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • DNA-Binding Proteins
  • I kappa B beta protein
  • I-kappa B Proteins
  • Immunosuppressive Agents
  • Lipopolysaccharides
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nfkbia protein, mouse
  • RNA, Messenger
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • NF-KappaB Inhibitor alpha
  • Interleukin-4
  • DNA