Roles of CCR2 and CCR5 for Hepatic Macrophage Polarization in Mice With Liver Parenchymal Cell-Specific NEMO Deletion.


Journal

Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302

Informations de publication

Date de publication:
2021
Historique:
received: 16 02 2020
revised: 27 08 2020
accepted: 31 08 2020
pubmed: 9 9 2020
medline: 21 12 2021
entrez: 8 9 2020
Statut: ppublish

Résumé

Macrophages are key regulators of inflammation and cancer promotion in the liver, and their recruitment and activation is linked to chemokine receptor signaling. However, the exact roles of the chemokine receptors CCR2 and CCR5 for macrophage functions in the liver is obscure. To study CCR2 and CCR5 in inflammatory liver injury, we used mice with a hepatocyte-specific knock-out of the nuclear factor κB (NF-κB) essential modulator (NEMO), termed NEMO We found that both CCR2 and CCR5 deficiency led to reduced fibrosis, while CCR5 deficiency increased steatosis and tumor burden in NEMO Although CCR2 and CCR5 principally promote liver fibrosis, they exert differential functions on hepatic macrophages during liver disease progression in NEMO

Sections du résumé

BACKGROUND & AIMS
Macrophages are key regulators of inflammation and cancer promotion in the liver, and their recruitment and activation is linked to chemokine receptor signaling. However, the exact roles of the chemokine receptors CCR2 and CCR5 for macrophage functions in the liver is obscure.
METHODS
To study CCR2 and CCR5 in inflammatory liver injury, we used mice with a hepatocyte-specific knock-out of the nuclear factor κB (NF-κB) essential modulator (NEMO), termed NEMO
RESULTS
We found that both CCR2 and CCR5 deficiency led to reduced fibrosis, while CCR5 deficiency increased steatosis and tumor burden in NEMO
CONCLUSIONS
Although CCR2 and CCR5 principally promote liver fibrosis, they exert differential functions on hepatic macrophages during liver disease progression in NEMO

Identifiants

pubmed: 32896623
pii: S2352-345X(20)30136-3
doi: 10.1016/j.jcmgh.2020.08.012
pmc: PMC7779787
pii:
doi:

Substances chimiques

CCR5 protein, mouse 0
Ccr2 protein, mouse 0
Intracellular Signaling Peptides and Proteins 0
NEMO protein, mouse 0
Receptors, CCR2 0
Receptors, CCR5 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

327-347

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Matthias Bartneck (M)

Department of Medicine III, RWTH Aachen University, Aachen, Germany.

Christiane Koppe (C)

Department of Medicine III, RWTH Aachen University, Aachen, Germany.

Viktor Fech (V)

Department of Medicine III, RWTH Aachen University, Aachen, Germany.

Klaudia T Warzecha (KT)

Department of Medicine III, RWTH Aachen University, Aachen, Germany.

Marlene Kohlhepp (M)

Department of Medicine III, RWTH Aachen University, Aachen, Germany; Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany.

Sebastian Huss (S)

Gerhard Domagk Institute of Pathology, University Hospital Münster, Münster, Germany.

Ralf Weiskirchen (R)

Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany.

Christian Trautwein (C)

Department of Medicine III, RWTH Aachen University, Aachen, Germany.

Tom Luedde (T)

Department of Medicine III, RWTH Aachen University, Aachen, Germany; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Frank Tacke (F)

Department of Medicine III, RWTH Aachen University, Aachen, Germany; Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany. Electronic address: frank.tacke@charite.de.

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Classifications MeSH