c-Fos suppresses systemic inflammatory response to endotoxin

Int Immunol. 2006 May;18(5):671-7. doi: 10.1093/intimm/dxl004. Epub 2006 Mar 28.


We explored the role of the transcription factor c-Fos in lipopolysaccharide (LPS)-induced cytokine response using mice lacking c-Fos (Fos-/- mice). Compared with wild-type controls, Fos-/- macrophages and mice showed significantly enhanced production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10. Bandshift analysis revealed that LPS-induced NF-kappaB binding activity to a functional site in the TNF-alpha promoter was significantly higher in Fos-/- than in wild-type macrophages. Using telemetry, we monitored body temperature and heart rate after LPS injection and found that Fos-/- mice undergo more severe hypothermia and bradycardia than wild-type mice. Such shock responses in Fos-/- mice were significantly reversed by neutralizing TNF-alpha. These data reveal a novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting through suppression of NF-kappaB activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Electrophoretic Mobility Shift Assay
  • Lipopolysaccharides / immunology*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Proto-Oncogene Proteins c-fos / deficiency
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / immunology*
  • Shock, Septic / immunology*
  • Shock, Septic / metabolism
  • Shock, Septic / prevention & control*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology


  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Proto-Oncogene Proteins c-fos
  • Tumor Necrosis Factor-alpha