c-Fos suppresses systemic inflammatory response to endotoxin

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

研究成果: Article査読

71 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)671-677
ページ数7
ジャーナルInternational immunology
18
5
DOI
出版ステータスPublished - 2006 5月 15

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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