CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis
Autor: | John Penders, Kai Markus Schneider, Wei Hu, Andreas Ludwig, Frank Tacke, Lijun Liao, Daniela Dreymueller, Nikolaus Gassler, Gernot Sellge, Veerle Bieghs, Oliver Pabst, Felix Heymann, Christian Trautwein, M. Frissen, Eicke Latz |
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Přispěvatelé: | Moleculaire Genetica, Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R2 - Gut-liver homeostasis, RS: CAPHRI - R4 - Health Inequities and Societal Participation |
Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Male
Blood Glucose Macrophage polarization CX3C Chemokine Receptor 1 Inflammation pharmacology [Anti-Bacterial Agents] metabolism [Intestinal Mucosa] microbiology [Intestines] Biology Gut flora Liver disease Mice Nonalcoholic fatty liver disease medicine Animals Homeostasis ddc:610 MACROPHAGES FATTY LIVER-DISEASE INSULIN-RESISTANCE Hepatology immunology [Non-alcoholic Fatty Liver Disease] NONALCOHOLIC STEATOHEPATITIS Microbiota GUT MICROBIOTA NLRP3 INFLAMMASOME ACTIVATION physiology [Macrophages] AKKERMANSIA-MUCINIPHILA medicine.disease biology.organism_classification metabolism [Non-alcoholic Fatty Liver Disease] Immunity Innate Anti-Bacterial Agents Mice Inbred C57BL Bacterial Translocation physiology [Receptors Chemokine] OBESITY Immunology METABOLIC DISEASE Increased inflammatory response Receptors Chemokine Steatohepatitis Metabolic syndrome medicine.symptom Cx3cr1 protein mouse analysis [Blood Glucose] FRACTALKINE/CX3CR1 SYSTEM |
Zdroj: | Hepatology, 62(5), 1405-1416. Wiley Hepatology 62(5), 1405-1416 (2015). doi:10.1002/hep.27982 |
ISSN: | 0270-9139 |
DOI: | 10.1002/hep.27982 |
Popis: | Nonalcoholic fatty liver disease is seen as the hepatic manifestation of the metabolic syndrome and represents the most common liver disease in Western societies. The G protein-coupled chemokine receptor CX3CR1 plays a central role in several metabolic syndrome-related disease manifestations and is involved in maintaining intestinal homeostasis. Because diet-induced intestinal dysbiosis is a driver for nonalcoholic fatty liver disease, we hypothesized that CX3CR1 may influence the development of steatohepatitis. In two independent models of diet-induced steatohepatitis (high-fat diet and methionine/choline-deficient diet), CX3CR1 protected mice from excessive hepatic steatosis and inflammation, as well as systemic glucose intolerance. Lack of Cx3cr1 expression was associated with significantly altered intestinal microbiota composition, which was linked to an impaired intestinal barrier. Concomitantly, endotoxin levels in portal serum and inflammatory macrophages in liver were increased in Cx3cr1(-/-) mice, indicating an increased inflammatory response. Depletion of intestinal microbiota by administration of broad-spectrum antibiotics suppressed the number of infiltrating macrophages and promoted macrophage polarization in liver. Consequently, antibiotic-treated mice demonstrated a marked improvement of steatohepatitis. Conclusion: Microbiota-mediated activation of the innate immune responses through CX3CR1 is crucial for controlling steatohepatitis progression, which recognizes CX3CR1 as an essential gatekeeper in this scenario. (Hepatology 2015;62:1405-1416) |
Databáze: | OpenAIRE |
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