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NLRP6 Inflammasome Modulates Disease Progression in a Chronic-Plus-Binge Mouse Model of Alcoholic Liver Disease.
- Source :
-
Cells [Cells] 2022 Jan 06; Vol. 11 (2). Date of Electronic Publication: 2022 Jan 06. - Publication Year :
- 2022
-
Abstract
- A considerable percentage of the population is affected by alcoholic liver disease (ALD). It is characterized by inflammatory signals from the liver and other organs, such as the intestine. The NLR family pyrin domain containing 6 (NLRP6) inflammasome complex is one of the most important inflammatory mediators. The aim of this study was to evaluate a novel mouse model for ALD characterized by 8-week chronic-plus-binge ethanol administration and to investigate the role of NLRP6 inflammasome for intestinal homeostasis and ALD progression using Nlrp6 <superscript>-/-</superscript> mice. We showed that chronic-plus-binge ethanol administration triggers hepatic steatosis, injury, and neutrophil infiltration. Furthermore, we discovered significant changes of intestinal microbial communities, including increased relative abundances of bacteria within the phyla Bacteroidota and Campilobacterota , as well as reduced Firmicutes . In this ALD model, inhibiting NLRP6 signaling had no effect on liver steatosis or damage, but had a minor impact on intestinal homeostasis via affecting intestinal epithelium function and gut microbiota. Surprisingly, Nlrp6 loss resulted in significantly decreased hepatic immune cell infiltration. As a result, our novel mouse model encompasses several aspects of human ALD, such as intestinal dysbiosis. Interfering with NLRP6 inflammasome activity reduced hepatic immune cell recruitment, indicating a disease-aggravating role of NLRP6 during ALD.
- Subjects :
- Alcohol Drinking
Animals
Binge-Eating Disorder microbiology
Cecum microbiology
Chronic Disease
Disease Models, Animal
Fatty Liver complications
Fatty Liver pathology
Gastrointestinal Microbiome
Intestinal Mucosa pathology
Liver injuries
Liver pathology
Liver Diseases, Alcoholic microbiology
Mice, Inbred C57BL
Mice, Knockout
Neutrophil Infiltration
Receptors, Cell Surface deficiency
Signal Transduction
Mice
Binge-Eating Disorder metabolism
Binge-Eating Disorder pathology
Disease Progression
Inflammasomes metabolism
Liver Diseases, Alcoholic metabolism
Liver Diseases, Alcoholic pathology
Receptors, Cell Surface metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 11
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 35053298
- Full Text :
- https://doi.org/10.3390/cells11020182