IL-10-mediated suppression of TNF-alpha production is independent of its ability to inhibit NF kappa B activity.
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.
Clarke
C J
CJ
Kennedy Institute of Rheumatology, Hammersmith, London, GB.
Hales
A
A
Hunt
A
A
Foxwell
B M
BM
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; D015847:Interleukin-4; D004247:DNA