| First Author | Das M | Year | 2009 |
| Journal | Cell | Volume | 136 |
| Issue | 2 | Pages | 249-60 |
| PubMed ID | 19167327 | Mgi Jnum | J:147632 |
| Mgi Id | MGI:3841849 | Doi | 10.1016/j.cell.2008.11.017 |
| Citation | Das M, et al. (2009) Induction of hepatitis by JNK-mediated expression of TNF-alpha. Cell 136(2):249-60 |
| abstractText | 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. |
