Journal
INTERNATIONAL IMMUNOLOGY
Volume 18, Issue 5, Pages 671-677Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxl004
Keywords
AP-1; body temperature; cytokines; knockout mice; NF-kappa B; telemetry; TNF-alpha
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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-kappa B 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-kappa B activity.
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