c-Fos suppresses systemic inflammatory response to endotoxin

Neelanjan Ray, Masayoshi Kuwahara, Yasunari Takada, Kenta Maruyama, Tomohiro Kawaguchi, Hirokazu Tsubone, Hiromichi Ishikawa, Koichi Matsuo

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56 Citations (Scopus)

Abstract

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)-α, interleukin (IL)-6 and IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10. Bandshift analysis revealed that LPS-induced NF-κB binding activity to a functional site in the TNF-α 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-α. These data reveal a novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting through suppression of NF-κB activity.

Original languageEnglish
Pages (from-to)671-677
Number of pages7
JournalInternational immunology
Volume18
Issue number5
DOIs
Publication statusPublished - 2006 May 15

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Keywords

  • AP-1
  • Body temperature
  • Cytokines
  • Knockout mice
  • NF-κB
  • TNF-α
  • Telemetry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ray, N., Kuwahara, M., Takada, Y., Maruyama, K., Kawaguchi, T., Tsubone, H., Ishikawa, H., & Matsuo, K. (2006). c-Fos suppresses systemic inflammatory response to endotoxin. International immunology, 18(5), 671-677. https://doi.org/10.1093/intimm/dxl004