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The role of PIM kinases in human and mouse CD4+ T cell activation and inflammatory bowel disease.

Jackson, Leila J; Pheneger, Jed A; Pheneger, Tracy J; Davis, Gregg; Wright, A Dale; Robinson, John E; Allen, Shelley; Munson, Mark C; Carter, Laura L.
Cell Immunol; 272(2): 200-13, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22078270
PIM kinases are a family of three serine/threonine kinases expressed following T cell activation. Using potent selective small molecule antagonists of PIM-1/3 kinases, we demonstrate a potential role for these enzymes in naïve and effector CD4+ T cell activation. PIM-1/3 inhibition prevented CD4+ T cell proliferation by inducing a G0/G1 cell cycle arrest without affecting cellular survival. In the absence of PIM-1/3 kinase activity, naïve CD4+ T cells failed to fully differentiate into effector cells both in vitro and in vivo. Therapeutic dosing of a PIM-1/3 inhibitor was efficacious in a CD4+ T cell-mediated model of inflammatory bowel disease suggesting that PIM-1 and PIM-3 kinase activity contributes to sustained disease severity. These results demonstrate that PIM-1/3 kinases have an important role in CD4+ T cell responses and inhibition of this activity may provide a therapeutic benefit in T cell-mediated diseases.
Selo DaSilva