Related Experiment Videos
c-Fos suppresses systemic inflammatory response to endotoxin
Neelanjan Ray1, Masayoshi Kuwahara, Yasunari Takada
1Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinanomachi, 160-8582 Tokyo, Japan.
International Immunology
|March 30, 2006
Summary
The transcription factor c-Fos acts as an anti-inflammatory agent by suppressing NF-kappaB activity. Mice lacking c-Fos exhibit heightened inflammatory responses and severe shock following lipopolysaccharide (LPS) exposure.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- The transcription factor c-Fos is involved in cellular responses to stimuli.
- Lipopolysaccharide (LPS) is a potent activator of inflammatory pathways.
Purpose of the Study:
- To investigate the role of c-Fos in the lipopolysaccharide (LPS)-induced cytokine response.
- To determine if c-Fos acts as an anti-inflammatory factor in vivo.
Main Methods:
- Utilized c-Fos knockout (Fos-/-) mice and wild-type controls.
- Assessed cytokine production (TNF-alpha, IL-6, IL-12 p40, IL-10) in macrophages and mice.
- Performed bandshift analysis to evaluate NF-kappaB binding activity.
- Monitored body temperature and heart rate using telemetry after LPS injection.
Main Results:
- Fos-/- macrophages and mice exhibited significantly enhanced production of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-12 p40) and reduced IL-10.
- LPS-induced NF-kappaB binding activity was significantly higher in Fos-/- macrophages.
- Fos-/- mice displayed more severe hypothermia and bradycardia after LPS challenge.
- Neutralizing TNF-alpha reversed the shock responses in Fos-/- mice.
Conclusions:
- c-Fos functions as an endogenous anti-inflammatory transcription factor.
- c-Fos suppresses NF-kappaB activity, thereby regulating the inflammatory cytokine response.
- Loss of c-Fos exacerbates LPS-induced inflammation and shock.