Induction of hepatitis by JNK-mediated expression of TNF-alpha
Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Digestive System Diseases | Molecular Biology
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 hematopoietic compartment exhibited a profound defect in hepatitis that was associated with markedly reduced expression of TNF-alpha. These data indicate that JNK is required for TNF-alpha expression but not for TNF-alpha-stimulated death of hepatocytes. Indeed, TNF-alpha 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.
DOI of Published Version
Cell. 2009 Jan 23;136(2):249-60. doi: 10.1016/j.cell.2008.11.017. Link to article on publisher's site
Das M, Sabio G, Jiang F, Rincon M, Flavell R, Davis RJ. (2009). Induction of hepatitis by JNK-mediated expression of TNF-alpha. Davis Lab Publications. https://doi.org/10.1016/j.cell.2008.11.017. Retrieved from https://escholarship.umassmed.edu/davis/75