Macrophage p38α promotes nutritional steatohepatitis through M1 polarization.
Animals
Cell Polarity
Chemokine CXCL10
/ metabolism
Diet, High-Fat
Disease Models, Animal
Disease Progression
Drug Discovery
Hepatocytes
/ metabolism
Humans
Interleukin-6
/ metabolism
Macrophage Activation
Macrophages
/ metabolism
Mice
Mice, Knockout
Non-alcoholic Fatty Liver Disease
/ immunology
Tumor Necrosis Factor-alpha
/ metabolism
p38 Mitogen-Activated Protein Kinases
/ antagonists & inhibitors
Hepatocytes
Macrophages
Pro-inflammatory cytokines
Steatohepatitis
p38 MAPK
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
09
08
2018
revised:
11
03
2019
accepted:
14
03
2019
pubmed:
28
3
2019
medline:
15
12
2020
entrez:
28
3
2019
Statut:
ppublish
Résumé
p38 mitogen-activated protein kinases are important inflammatory factors. p38α alteration has been implicated in both human and mouse inflammatory disease models. Therefore, we aimed to characterize the cell type-specific role of p38α in non-alcoholic steatohepatitis (NASH). Human liver tissues were obtained from 27 patients with non-alcoholic fatty liver disease (NAFLD) and 20 control individuals. NASH was established and compared between hepatocyte-specific p38α knockout (p38α p38α was significantly upregulated in the liver tissues of patients with NAFLD. Compared to p38α Macrophage p38α promotes the progression of steatohepatitis by inducing pro-inflammatory cytokine secretion and M1 polarization. p38 inhibition protects against steatohepatitis. LAY SUMMARY: p38 mitogen-activated protein kinases are important inflammatory factors. In the present study, we demonstrated that p38α is upregulated in liver tissues of patients with non-alcoholic fatty liver diseases. Genetic deletion of p38α in macrophages led to ameliorated nutritional steatohepatitis in mice through decreased pro-inflammatory cytokine secretion and increased M2 macrophage polarization.
Sections du résumé
BACKGROUND & AIMS
p38 mitogen-activated protein kinases are important inflammatory factors. p38α alteration has been implicated in both human and mouse inflammatory disease models. Therefore, we aimed to characterize the cell type-specific role of p38α in non-alcoholic steatohepatitis (NASH).
METHODS
Human liver tissues were obtained from 27 patients with non-alcoholic fatty liver disease (NAFLD) and 20 control individuals. NASH was established and compared between hepatocyte-specific p38α knockout (p38α
RESULTS
p38α was significantly upregulated in the liver tissues of patients with NAFLD. Compared to p38α
CONCLUSIONS
Macrophage p38α promotes the progression of steatohepatitis by inducing pro-inflammatory cytokine secretion and M1 polarization. p38 inhibition protects against steatohepatitis. LAY SUMMARY: p38 mitogen-activated protein kinases are important inflammatory factors. In the present study, we demonstrated that p38α is upregulated in liver tissues of patients with non-alcoholic fatty liver diseases. Genetic deletion of p38α in macrophages led to ameliorated nutritional steatohepatitis in mice through decreased pro-inflammatory cytokine secretion and increased M2 macrophage polarization.
Identifiants
pubmed: 30914267
pii: S0168-8278(19)30184-9
doi: 10.1016/j.jhep.2019.03.014
pii:
doi:
Substances chimiques
Chemokine CXCL10
0
Interleukin-6
0
Tumor Necrosis Factor-alpha
0
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
163-174Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2019 European Association for the Study of the Liver. All rights reserved.