[HTML][HTML] Induction of hepatitis by JNK-mediated expression of TNF-α
Cell, 2009•cell.com
The c-Jun NH 2-terminal kinase (JNK) signaling pathway has been implicated in the
development of tumor necrosis factor (TNF)-dependent hepatitis. JNK may play a critical role
in hepatocytes during TNF-stimulated cell death in vivo. To test this hypothesis, we
examined the phenotype of mice with compound disruption of the Jnk1 and Jnk2 genes.
Mice with loss of JNK1/2 expression in hepatocytes exhibited no defects in the development
of hepatitis compared with control mice, whereas mice with loss of JNK1/2 in the …
development of tumor necrosis factor (TNF)-dependent hepatitis. JNK may play a critical role
in hepatocytes during TNF-stimulated cell death in vivo. To test this hypothesis, we
examined the phenotype of mice with compound disruption of the Jnk1 and Jnk2 genes.
Mice with loss of JNK1/2 expression in hepatocytes exhibited no defects in the development
of hepatitis compared with control mice, whereas mice with loss of JNK1/2 in the …
Summary
The c-Jun NH2-terminal kinase (JNK) signaling pathway has been implicated in the development of tumor necrosis factor (TNF)-dependent hepatitis. JNK may play a critical role in hepatocytes during TNF-stimulated cell death in vivo. To test this hypothesis, we examined the phenotype of mice with compound disruption of the Jnk1 and Jnk2 genes. Mice with loss of JNK1/2 expression in hepatocytes exhibited no defects in the development of hepatitis compared with control mice, whereas mice with loss of JNK1/2 in the hematopoietic compartment exhibited a profound defect in hepatitis that was associated with markedly reduced expression of TNF-α. These data indicate that JNK is required for TNF-α expression but not for TNF-α-stimulated death of hepatocytes. Indeed, TNF-α induced similar hepatic damage in both mice with hepatocyte-specific JNK1/2 deficiency and control mice. These observations confirm a role for JNK in the development of hepatitis but identify hematopoietic cells as the site of the essential function of JNK.
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