IL-17A-mediated ERK1/2/p65 signaling pathway is associated with cell apoptosis after non-alcoholic steatohepatitis

Ya-Jie Pan; Xing Ren; Ying-Ying Zhang; Jun Lv; Qing-Lei Zeng; Hong-Yu Zhang; Zu-Jiang Yu

doi:10.1002/iub.1960

IL-17A-mediated ERK1/2/p65 signaling pathway is associated with cell apoptosis after non-alcoholic steatohepatitis

IUBMB Life. 2019 Mar;71(3):302-309. doi: 10.1002/iub.1960. Epub 2018 Nov 27.

Authors

Ya-Jie Pan¹, Xing Ren², Ying-Ying Zhang¹, Jun Lv¹, Qing-Lei Zeng¹, Hong-Yu Zhang¹, Zu-Jiang Yu¹

Affiliations

¹ Department of Infectious Diseases and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
² Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

PMID: 30481403
DOI: 10.1002/iub.1960

Abstract

Interleukin (IL)-17A is pro-inflammatory cytokine which has been identified as a noninvasive marker of the pathogenesis of non-alcoholic steatohepatitis (NASH). However, the underlying role of IL-17A in NASH progression remains unclear. This study was designed to investigate the biological function and molecular mechanism of IL-17A in the induction of NASH. The results showed that IL-17A was highly expressed in high-fat diet (HFD)-induced NASH mouse model. Intravenous injection of IL-17A exacerbated steatohepatitis process via promoting hepatocyte apoptosis. Furthermore, IL-17A-induced apoptosis was mediated by ERK1/2/p65 signaling pathway. In conclusion, we demonstrated that IL-17A-mediated ERK1/2/p65 signaling pathway was a promising target for the treatment of NASH. © 2018 IUBMB Life, 71(3):302-309, 2019.

Keywords: ERK1/2; IL-17A; NSAH; p65.

MeSH terms

Animals
Apoptosis / genetics*
Diet, High-Fat / adverse effects
Disease Models, Animal
Disease Progression
Gene Expression Regulation
Hepatocytes / metabolism
Hepatocytes / pathology
Interleukin-17 / administration & dosage
Interleukin-17 / blood
Interleukin-17 / genetics*
Liver / metabolism
Liver / pathology
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 1 / genetics*
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / genetics*
Mitogen-Activated Protein Kinase 3 / metabolism
Non-alcoholic Fatty Liver Disease / etiology
Non-alcoholic Fatty Liver Disease / genetics*
Non-alcoholic Fatty Liver Disease / metabolism
Non-alcoholic Fatty Liver Disease / pathology
Signal Transduction
Transcription Factor RelA / genetics*
Transcription Factor RelA / metabolism

Substances

Il17a protein, mouse
Interleukin-17
Rela protein, mouse
Transcription Factor RelA
Mapk1 protein, mouse
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3