| First Author | Ray N | Year | 2006 |
| Journal | Int Immunol | Volume | 18 |
| Issue | 5 | Pages | 671-7 |
| PubMed ID | 16569682 | Mgi Jnum | J:108901 |
| Mgi Id | MGI:3625250 | Doi | 10.1093/intimm/dxl004 |
| Citation | Ray N, et al. (2006) c-Fos suppresses systemic inflammatory response to endotoxin. Int Immunol 18(5):671-7 |
| abstractText | 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. |
