The role of p53 and Fas in a model of acute murine graft-versus-host disease.

Graft-vs-host disease (GVHD) is a devastating, frequently fatal, pathological condition associated with lesions in specific target organs, including the intestine, liver, lung, and skin, as well as pancytopenia and alopecia. Bone marrow (BM) atrophy is observed in acutely diseased animals, but the underlying mechanisms of hemopoietic stem cell depletion remained to be established. We used an experimental mouse model of acute GVHD in which parental cells were injected into F(1) hosts preconditioned by sublethal irradiation.

Hypothermia inhibits Fas-mediated apoptosis of primary mouse hepatocytes in culture.

Apoptosis occurs during the isolation and even short-term storage and culture of hepatocytes, and in the pathogenesis of liver diseases, such as hepatic failure and hepatitis. Therapeutic hypothermia has beneficial effects in experimental models of fulminant hepatic failure. The mechanisms underlying the potential benefits of mild hypothermia on the liver have not been well investigated.

Radiation-induced crypt intestinal epithelial cell apoptosis in vivo involves both caspase-3-dependent and -independent pathways.

Caspases play a major role in virtually all forms of apoptosis. Radiation is well known to induce apoptosis of crypt intestinal epithelial cells (IEC). Here, we examined the role of caspase-3 in radiation-induced IEC apoptosis.

Nonlymphoid Fas ligand in peptide-induced peripheral lymphocyte deletion.

Peripheral lymphocyte deletion is required for reduction of lymphocyte numbers after expansion in response to antigen. Peripheral deletion is mediated in part by the activation of apoptosis by engagement of the death receptor, Fas (CD95), by its ligand, Fas ligand (FasL; CD95L), among other mechanisms. Here we used T cell receptor (TCR) transgenic animals to examine the role of inducible expression of nonlymphoid FasL in response to peptide antigen.

Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis.

The role of the tumor suppressor p53 as a key regulator of inflammation was examined in murine collagen-induced arthritis (CIA), a model of rheumatoid arthritis. Wild-type DBA/1 mice develop progressive arthritis in this model, in which p53 expression and apoptosis are evident in the synovial cells. In contrast, the joints of p53(-/-) DBA/1 animals with CIA showed increased severity of arthritis using clinical and histological scoring methods with almost no apoptosis.