This study aimed to investigate whether the classic hepatoprotective drug polyene phosphatidylcholine (PPC) regulates macrophage polarization and explores the potential role of TLR-2 in this process. In RAW264.7 macrophages and murine bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS), PPC significantly inhibited the production of IL-6, TNF-α, and the mRNA expression of M1-type macrophage markers. Consistently, PPC reduced the mRNA expression of several key enzymes in the pathways of glycolysis and lipid synthesis while increasing the expression of key enzymes associated with lipid oxidation. Moreover, blocking the glycolytic pathway using 2-deoxy-D-glucose (2-DG) significantly enhanced the anti-inflammatory effect of PPC. However, inhibition of lipid oxidation using GW9662 (an inhibitor of PPAR-γ) and GW6471 (an inhibitor of PPAR-α) abolished the anti-inflammatory effect of PPC. Interestingly, TLR-2 expression in macrophages was significantly downregulated after exposure to PPC. Moreover, pre-activation of TLR-2 hampered the anti-inflammatory effect of PPC. In addition, PPC did not inhibit the secretion of IL-6 and TNF-α in TLR-2-/- BMDMs that were activated by LPS. This was consistent with the increased expression of M1 markers and glycolytic and lipid synthesis enzymes but decreased lipid oxidation-related enzymes. These results showed that PPC inhibits the differentiation of M1-type macrophages, which was most likely related to TLR-2-mediated metabolic reprogramming.

中文翻译：

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TLR-2介导的代谢重编程参与多烯磷脂酰胆碱介导的M1巨噬细胞极化抑制。

这项研究旨在调查经典的保肝药物多烯磷脂酰胆碱（PPC）是否调节巨噬细胞极化，并探讨TLR-2在此过程中的潜在作用。在脂多糖（LPS）刺激的RAW264.7巨噬细胞和鼠源性骨髓巨噬细胞（BMDM）中，PPC显着抑制IL-6，TNF-α的产生以及M1型巨噬细胞标志物的mRNA表达。一致地，PPC减少了糖酵解和脂质合成途径中几种关键酶的mRNA表达，同时增加了与脂质氧化相关的关键酶的表达。而且，使用2-脱氧-D-葡萄糖（2-DG）阻断糖酵解途径显着增强了PPC的抗炎作用。然而，使用GW9662（PPAR-γ的抑制剂）和GW6471（PPAR-α的抑制剂）抑制脂质氧化消除了PPC的抗炎作用。有趣的是，巨噬细胞中的TLR-2表达在暴露于PPC后显着下调。此外，TLR-2的预激活阻碍了PPC的抗炎作用。此外，PPC不会抑制被LPS激活的TLR-2-/-BMDM中IL-6和TNF-α的分泌。这与M1标记和糖酵解及脂质合成酶的表达增加但与脂质氧化相关的酶减少有关。这些结果表明，PPC抑制M1型巨噬细胞的分化，这很可能与TLR-2介导的代谢重编程有关。暴露于PPC后巨噬细胞中的TLR-2表达显着下调。此外，TLR-2的预激活阻碍了PPC的抗炎作用。此外，PPC不会抑制被LPS激活的TLR-2-/-BMDM中IL-6和TNF-α的分泌。这与M1标记和糖酵解及脂质合成酶的表达增加但与脂质氧化相关的酶减少有关。这些结果表明，PPC抑制M1型巨噬细胞的分化，这很可能与TLR-2介导的代谢重编程有关。暴露于PPC后巨噬细胞中的TLR-2表达显着下调。此外，TLR-2的预激活阻碍了PPC的抗炎作用。此外，PPC不会抑制被LPS激活的TLR-2-/-BMDM中IL-6和TNF-α的分泌。这与M1标记和糖酵解及脂质合成酶的表达增加但与脂质氧化相关的酶减少有关。这些结果表明，PPC抑制M1型巨噬细胞的分化，这很可能与TLR-2介导的代谢重编程有关。这与M1标记和糖酵解及脂质合成酶的表达增加但与脂质氧化相关的酶减少有关。这些结果表明，PPC抑制M1型巨噬细胞的分化，这很可能与TLR-2介导的代谢重编程有关。这与M1标记和糖酵解及脂质合成酶的表达增加但与脂质氧化相关的酶减少有关。这些结果表明，PPC抑制M1型巨噬细胞的分化，这很可能与TLR-2介导的代谢重编程有关。