P38 alpha MAPK inhibits JNK activation and collaborates with IkappaB kinase 2 to prevent endotoxin-induced liver failure.

ABSTRACT: Activation of c-Jun amino-terminal kinase (JNK) facilitates tumour necrosis factor (TNF)-induced cell death. The p38 mitogen-activated protein kinase pathway is induced by TNF stimulation, but it has not been implicated in TNF-induced cell death. Here, we show that hepatocyte-specific ablation of p38alpha in mice results in excessive activation of JNK in the liver after in vivo challenge with bacterial lipopolysaccharide (LPS). Despite increased JNK activity, p38alpha-deficient hepatocytes were not sensitive to LPS/TNF toxicity showing that JNK activation was not sufficient to mediate TNF-induced liver damage. By contrast, LPS injection caused liver failure in mice lacking both p38alpha and IkappaB kinase 2 (IKK2) in hepatocytes. Therefore, when combined with partial nuclear factor-kappaB

SUBMITTER: Heinrichsdorff J 

PROVIDER: S-EPMC2572111 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature