Fos proteins suppress dextran sulfate sodium-induced colitis through inhibition of NF-kappaB.

The Fos family proteins, c-Fos and Fra-1, are components of the dimeric transcription factor AP-1, which is typically composed of Fos and Jun family proteins. We have previously shown that mice lacking c-Fos (Fos(-/-) mice) respond more strongly to LPS injection than do wild-type (wt) controls. We then examined the sensitivity of Fos(-/-) mice to acute inflammatory stress in a dextran sulfate sodium (DSS)-induced colitis model.

c-Fos-deficient mice are susceptible to Salmonella enterica serovar Typhimurium infection.

c-Fos is a component of transcription factor AP-1. We show that macrophages lacking c-Fos exhibit enhanced production of proinflammatory cytokines, potentiated NF-kappaB phosphorylation, and increased cell death following Salmonella enterica serovar Typhimurium infection. Furthermore, mice lacking c-Fos are highly susceptible to infection, suggesting that c-Fos confers resistance to Salmonella infection in mice.

Receptor activator of NF-kappa B ligand and osteoprotegerin regulate proinflammatory cytokine production in mice.

Receptor activator of NF-kappaB ligand (RANKL) is a membrane-bound or soluble cytokine essential for osteoclast differentiation, whereas the decoy receptor osteoprotegerin (OPG) masks RANKL activity. In mouse serum, both soluble RANKL and OPG are detectable. We observed that mice injected with LPS showed significantly down-regulated serum RANKL levels, whereas serum OPG levels were up-regulated.

c-Fos suppresses systemic inflammatory response to endotoxin.

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.

Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation.

Impaired Ag-presenting function in dendritic cells (DCs) due to abnormal differentiation is an important mechanism of tumor escape from immune control. A major role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR1/Flt-1 and VEGFR2/KDR/Flk-1, has been documented in hemopoietic development. To study the roles of each of these receptors in DC differentiation, we used an in vitro system of myeloid DC differentiation from murine embryonic stem cells.

Osteoclasts, mononuclear phagocytes, and c-Fos: new insight into osteoimmunology.

Osteoimmunology is the emerging concept that certain molecules link the skeletal and immune systems. The transcription factor c-Fos, a component of activator protein-1 (AP-1), is essential for osteoclast differentiation. Mice lacking c-Fos are osteopetrotic owing to impaired osteoclast development.