Abstract：
Mono-(2-ethylhexyl) phthalate (MEHP) can accumulate in the liver and then lead to hepatic steatosis, while the underlying mechanism remains unclear. Inflammation plays an important role in the disorder of hepatic lipid metabolism. This study aims to clarify the role of the inflammatory response mediated by formyl peptide receptor 2 (FPR2) in steatosis of L02 cells exposed to MEHP. L02 cells were exposed to MEHP of different concentrations and different time. A steatosis model of L02 cells was induced with oleic acid and the cells were exposed to MEHP simultaneously. In addition, L02 cells were incubated with FPR2 antagonist and then exposed to MEHP. Lipid accumulation was determined by oil red O staining and extraction assay. The indicators related to lipid metabolism and inflammatory response were measured with appropriate kits. The relative expression levels of FPR2 and its ligand were determined by Western blot, and the interaction of them was detected by co-immunoprecipitation. As a result, MEHP exposure could promote the occurrence and progression of steatosis and the secretion of chemokines and inflammatory factors in L02 cells. MEHP could also affect the expression and activation of FPR2 and the secretion of FPR2 ligands. In addition, the promotion effect of MEHP on the secretion of total cholesterol and interleukin 1β in L02 cells could be significantly inhibited by the FPR2 antagonist. We concluded that FPR2 might affect the promotion effect of MEHP on steatosis of L02 cells by mediating inflammatory response.
摘要：
邻苯二甲酸单（2-乙基己基）酯（MEHP）可以在肝脏中积累，然后导致肝脏脂肪变性，而潜在的机制仍不清楚。炎症在肝脏脂质代谢紊乱中起着重要作用。本研究旨在阐明甲酰肽受体2(FPR2)介导的炎症反应在MEHP暴露的L02细胞脂肪变性中的作用。将L02细胞暴露于不同浓度和不同时间的MEHP。用油酸诱导L02细胞的脂肪变性模型,并将细胞同时暴露于MEHP。此外,将L02细胞与FPR2拮抗剂一起孵育,然后暴露于MEHP。通过油红O染色和提取测定确定脂质积累。使用适当的试剂盒测量与脂质代谢和炎症反应相关的指标。Westernblot检测FPR2及其配体的相对表达水平,并通过免疫共沉淀检测它们之间的相互作用。因此,MEHP暴露可促进L02细胞脂肪变性的发生和发展以及趋化因子和炎症因子的分泌。MEHP还可以影响FPR2的表达和激活以及FPR2配体的分泌。此外,FPR2拮抗剂可显著抑制MEHP对L02细胞总胆固醇和白细胞介素1β分泌的促进作用。我们得出结论，FPR2可能通过介导炎症反应影响MEHP对L02细胞脂肪变性的促进作用。
