Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage.
Acetaminophen
Aged
Animals
Carbon Tetrachloride
Case-Control Studies
Female
Hematopoietic Stem Cells
/ metabolism
Hepatocytes
/ metabolism
Humans
Inflammation Mediators
/ metabolism
Kupffer Cells
/ metabolism
Lipid Peroxidation
/ physiology
Liver
/ metabolism
Liver Cirrhosis
/ etiology
Liver Cirrhosis, Experimental
/ immunology
Male
Membrane Glycoproteins
/ deficiency
Mice, Knockout
Middle Aged
Reactive Oxygen Species
/ metabolism
Receptors, Immunologic
/ deficiency
Toll-Like Receptor 4
/ physiology
Up-Regulation
/ physiology
acute liver failure
chronic liver disease
hepatic stellate cell
immune-mediated liver damage
inflammation
Journal
Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
07
03
2017
revised:
26
12
2017
accepted:
28
12
2017
pubmed:
29
1
2018
medline:
14
7
2020
entrez:
29
1
2018
Statut:
ppublish
Résumé
Liver injury impacts hepatic inflammation in part via Toll-like receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM-2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages but its function in liver injury is unknown. Here we hypothesised that the anti-inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury. TREM-2 expression was analysed in livers of humans with various forms of liver injury compared with control individuals. Acute and chronic liver injury models were performed in wild type and TREM-2 was expressed on non-parenchymal hepatic cells and induced during liver injury in mice and man. Mice lacking TREM-2 exhibited heightened liver damage and inflammation during acute and repetitive carbon tetrachloride and acetaminophen (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably associated with worsened survival. Liver damage in Our data indicate that by acting as a natural brake on inflammation during hepatocellular injury, TREM-2 is a critical regulator of diverse types of hepatotoxic injury.
Identifiants
pubmed: 29374630
pii: gutjnl-2017-314107
doi: 10.1136/gutjnl-2017-314107
pmc: PMC6580759
doi:
Substances chimiques
Inflammation Mediators
0
Membrane Glycoproteins
0
Reactive Oxygen Species
0
Receptors, Immunologic
0
TREM2 protein, human
0
Tlr4 protein, mouse
0
Toll-Like Receptor 4
0
Trem2 protein, mouse
0
Acetaminophen
362O9ITL9D
Carbon Tetrachloride
CL2T97X0V0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
533-546Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K001949/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L016354/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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