Reference - Detail
| RRC ID | 39512 |
|---|---|
| Author | Denaës T, Lodder J, Chobert MN, Ruiz I, Pawlotsky JM, Lotersztajn S, Teixeira-Clerc F. |
| Title | The Cannabinoid Receptor 2 Protects Against Alcoholic Liver Disease Via a Macrophage Autophagy-Dependent Pathway. |
| Journal | Sci Rep |
| Abstract |
Kupffer cells, the resident macrophages of the liver, play a major role in the pathogenesis of alcoholic liver disease. We have previously demonstrated that CB2 receptor protects against alcoholic liver disease by inhibiting alcohol-induced inflammation and steatosis via the regulation of Kupffer cell activation. Here, we explored the mechanism underlying these effects and hypothesized that the anti-inflammatory properties of CB2 receptor in Kupffer cells rely on activation of autophagy. For this purpose, mice invalidated for CB2 receptor (CB2(Mye-/-) mice) or for the autophagy gene ATG5 (ATG5(Mye-/-) mice) in the myeloid lineage, and their littermate wild-type mice were subjected to chronic-plus-binge ethanol feeding. CB2(Mye-/-) mice showed exacerbated alcohol-induced pro-inflammatory gene expression and steatosis. Studies in cultured macrophages demonstrated that CB2 receptor activation by JWH-133 stimulated autophagy via a heme oxygenase-1 dependent pathway. Moreover, JWH-133 reduced the induction of inflammatory genes by lipopolysaccharide in wild-type macrophages, but not in ATG5-deficient cells. The CB2 agonist also protected from alcohol-induced liver inflammation and steatosis in wild-type mice, but not in ATG5(Mye-/-) mice demonstrating that macrophage autophagy mediates the anti-inflammatory and anti-steatogenic effects of CB2 receptor. Altogether these results demonstrate that CB2 receptor activation in macrophages protects from alcohol-induced steatosis by inhibiting hepatic inflammation through an autophagy-dependent pathway. |
| Volume | 6 |
| Pages | 28806 |
| Published | 2016-6-27 |
| DOI | 10.1038/srep28806 |
| PII | srep28806 |
| PMID | 27346657 |
| PMC | PMC4921859 |
| MeSH | Alleles Animals Anti-Inflammatory Agents / chemistry Autophagy* Autophagy-Related Protein 5 / genetics Cell Lineage Ethanol / chemistry Fatty Liver / metabolism Heme Oxygenase-1 / metabolism Hepatitis, Alcoholic / metabolism Inflammation Lipopolysaccharides / chemistry Liver / metabolism Liver Diseases, Alcoholic / metabolism* Liver Diseases, Alcoholic / pathology Liver Diseases, Alcoholic / prevention & control Macrophages / metabolism* Male Membrane Proteins / metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Phenotype RAW 264.7 Cells Receptor, Cannabinoid, CB2 / agonists Receptor, Cannabinoid, CB2 / genetics* Receptor, Cannabinoid, CB2 / metabolism* |
| IF | 3.998 |
| Times Cited | 32 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 17 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00806 |