Kupffer细胞分泌的趋化因子CCL4诱导肝脏脂质合成基因的表达

Kupffer Cells-secreted Chemokine CCL4 Induces the Expression of Lipogenic Genes in Liver

肝脏中Kupffer细胞所介导的炎症反应在非酒精性脂肪肝病发生的过程中具有重要的作用.通过肝脏切片的苏木精-伊红染色观察,发现清除肝脏中的Kupffer细胞能有效地改善由高脂饮食所诱导的脂肪肝症状;通过实时荧光定量PCR检测,发现Kupffer细胞分泌的细胞因子CCL4基因的表达水平与脂肪肝密切相关,在脂肪肝模型小鼠肝脏中CCL4基因的表达水平显著上升;进一步利用CCL4重组蛋白体外处理,发现CCL4能诱导肝内脂质合成相关基因的表达,而CCL4受体的抑制剂Maraviroc能拮抗CCL4对肝细胞中脂质合成基因表达的诱导作用.综上结果可知,Kupffer细胞分泌的CCL4可通过CCR5信号通路诱导肝细胞脂质合成基因的表达.

Kupffer cells-mediated inflammation response plays an important role in non-alcoholic fatty liver disease（NAFLD）.In this study,using HE staining to analyze the liver structure,we found that depletion of Kupffer cells ameliorated the hepatic steatosis induced by high fat diet.In addition,CCL4,a cytokines secreted by Kupffer cells,was associated with NAFLD development,as the qRT-PCR results showed that the expression of CCL4 gene was elevated in the liver of NAFLD mice.Moreover,under the treatment by CCL4 recombinant protein,it showed an induction on the expression of the lipogenic genes,which was antagonized by Maraviroc,an established inhibitor of CCL4 downstream receptor CCR5.Taking together,it is suggested that CCL4 secreted by Kupffer cells and its receptor CCR5 participate in the regulation of hepatic lipogenesis by inflammation response in liver.