Blockade of IL-17 signaling reverses alcohol-induced liver injury and excessive alcohol drinking in mice.
Alcohol Drinking
Animals
Astrocytes
/ immunology
Ethanol
/ administration & dosage
Humans
Interleukin-17
/ blood
Liver Diseases, Alcoholic
/ metabolism
Male
Mice
Mice, Inbred C57BL
Microglia
/ immunology
Nuclear Receptor Subfamily 1, Group F, Member 3
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Addiction
Fibrosis
Gastroenterology
Mouse models
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
13 02 2020
13 02 2020
Historique:
received:
10
07
2019
accepted:
26
12
2019
entrez:
14
2
2020
pubmed:
14
2
2020
medline:
22
6
2021
Statut:
epublish
Résumé
Chronic alcohol abuse has a detrimental effect on the brain and liver. There is no effective treatment for these patients, and the mechanism underlying alcohol addiction and consequent alcohol-induced damage of the liver/brain axis remains unresolved. We compared experimental models of alcoholic liver disease (ALD) and alcohol dependence in mice and demonstrated that genetic ablation of IL-17 receptor A (IL-17ra-/-) or pharmacological blockade of IL-17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL-17A positively correlated with the alcohol use in excessive drinkers and was further increased in patients with ALD as compared with healthy individuals. Our data suggest that IL-17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL-17A may provide a novel strategy for treatment of alcohol-induced pathology.
Identifiants
pubmed: 32051339
pii: 131277
doi: 10.1172/jci.insight.131277
pmc: PMC7098802
doi:
pii:
Substances chimiques
IL17A protein, human
0
Il17a protein, mouse
0
Interleukin-17
0
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAAA NIH HHS
ID : R21 AA024935
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS093055
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES010337
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS054734
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA025208
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA100660
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026685
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI043477
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA024198
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK099205
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA022614
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA027681
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA011999
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA006420
Pays : United States
Organisme : CSRD VA
ID : I01 CX000361
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI043477
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA021491
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA020864
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101737
Pays : United States
Organisme : RRD VA
ID : I01 RX002483
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA234128
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107682
Pays : United States
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