Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury.
Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury.
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DOI：
10.1016/j.jnutbio.2013.02.001
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Feng W
中科院分区：
文献类型：
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作者：
Wang Y;Liu Y;Kirpich I;Ma Z;Wang C;Zhang M;Suttles J;McClain C;Feng W
益生菌治疗酒精性肝病（ALD）的治疗效果已经在患者和实验动物模型中进行了研究。虽然ALD发病机制的确切机制还不完全清楚，但肠源性内毒素已被假定在肝脏炎症中起关键作用。先前的研究已经证明，益生菌疗法减少了ALD患者肠道革兰氏阴性菌来源的循环内毒素。在这项研究中，我们研究了益生菌对慢性酒精摄入引起的肝脏肿瘤坏死因子-α（TNFα）产生和炎症的影响。给小鼠喂食含有5%酒精的Lieber deCarli液体饮食8周，并在最后几周补充鼠李糖乳杆菌GG（LGG）。8周酒精喂养引起肝脏炎症的显着增加，如组织学评估和肝组织髓过氧化物酶活性测定所示。两周的LGG补充减少肝脏炎症和肝损伤，并显着降低TNFα的表达。酒精喂养增加肝脏Toll样受体和CYP 2 E1的mRNA表达，降低核因子红细胞2相关因子2的表达。LGG补充减弱了这些变化。使用人外周血单核细胞衍生的巨噬细胞，我们还证明了与乙醇孵育引发脂多糖和鞭毛蛋白诱导的TNFα产生，LGG培养上清液以剂量依赖性方式降低了这种诱导。此外，LGG治疗也显着降低酒精诱导的p38 MAP激酶的磷酸化。总之，益生菌LGG治疗通过抑制TLR 4和TLR 5介导的内毒素活化减弱TNFα的产生来减少酒精诱导的肝脏炎症。
The therapeutic effects of probiotic treatment in alcoholic liver disease (ALD) have been studied in both patients and experimental animal models. Although the precise mechanisms of the pathogenesis of ALD are not fully understood, gut-derived endotoxin has been postulated to play a crucial role in hepatic inflammation. Previous studies have demonstrated that probiotic therapy reduces circulating endotoxin derived from intestinal Gram-negative bacteria in ALD. In this study, we investigated the effects of probiotics on hepatic tumor necrosis factor-α (TNFα) production and inflammation in response to chronic alcohol ingestion. Mice were fed Lieber deCarli liquid diet containing 5% alcohol for 8 weeks and Lactobacillus rhamnosus GG (LGG) was supplemented in the last weeks. Eight-week alcohol feeding caused a significant increase in hepatic inflammation as shown by histological assessment and hepatic tissue myeloperoxidase activity assay. Two-weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNFα expression. Alcohol feeding increased hepatic mRNA expression of Toll-like receptors and CYP2E1 and decreased nuclear factor erythroid 2-related factor 2 expression. LGG supplementation attenuated these changes. Using human peripheral blood monocytes-derived macrophages we also demonstrated that incubation with ethanol primes both lipopolysaccharide- and flagellin-induced TNFα production, and LGG culture supernatant reduced this induction in a dose dependent manner. In addition, LGG treatment also significantly decreased alcohol-induced phosphorylation of p38 MAP kinase. In conclusion, probiotic LGG treatment reduced alcohol-induced hepatic inflammation by attenuation of TNFα production via inhibition of TLR4 and TLR5-mediated endotoxin activation.