Inflammation Mediated by JNK in Myeloid Cells Promotes the Development of Hepatitis and Hepatocellular Carcinoma

Cell Rep. 2016 Apr 5;15(1):19-26. doi: 10.1016/j.celrep.2016.03.008. Epub 2016 Mar 24.

Abstract

The cJun NH2-terminal kinase (JNK) signaling pathway is required for the development of hepatitis and hepatocellular carcinoma. A role for JNK in liver parenchymal cells has been proposed, but more recent studies have implicated non-parenchymal liver cells as the relevant site of JNK signaling. Here, we tested the hypothesis that myeloid cells mediate this function of JNK. We show that mice with myeloid cell-specific JNK deficiency exhibit reduced hepatic inflammation and suppression of both hepatitis and hepatocellular carcinoma. These data identify myeloid cells as a site of pro-inflammatory signaling by JNK that can promote liver pathology. Targeting myeloid cells with a drug that inhibits JNK may therefore provide therapeutic benefit for the treatment of inflammation-related liver disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism*
  • Hepatitis / metabolism*
  • Inflammation / metabolism
  • Liver Neoplasms / metabolism*
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / metabolism*

Substances

  • MAP Kinase Kinase 4