Work

The protein tyrosine kinase SYK regulates the alternative p38 activation in liver during acute liver inflammation

Year: 2019

Type: article

Abstract: Two distinct p38 signaling pathways, classical and alternative, have been identified to regulate inflammatory responses in host defense and disease development. The role of alternative p38 activation in liver inflammation is elusive, while classical p38 signaling in hepatocytes plays a role in regulating the induction of cell death in autoimmune-mediated acute liver injury. In this study, we found that a mutation of alternative p38 in mice augmented the severity of acute liver inflammation. Moreover, TNF-induced hepatocyte death was augmented by a mutation of alternative p38, suggesting that alternative p38 signaling in hepatocytes contributed more significantly to the pathology of acute liver injury. Furthermore, SYK-Vav-1 signaling regulates alternative p38 activation and the downregulation of cell death in hepatocytes. Therefore, it is suggested that alternative p38 signaling in the liver plays a critical role in the induction and subsequent pathological changes of acute liver injury. Collectively, our results imply that p38 signaling in hepatocytes plays a crucial role to prevent excessive liver injury by regulating the induction of cell death and inflammation.

Source: Scientific Reports

DOI: 10.1038/s41598-019-54335-3

Authors: Bo-Ram Bang, Kyung Ho Han, Goo-Young Seo, Michael Croft, Young Jun Kang

Institutions: University of Southern California, Scripps Research Institute, La Jolla Institute for Immunology, Molecular Medicine Research Institute

Language: English

Topic: Liver physiology and pathology

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,790