Pan Wei, Hao Wen-Ting, Xu Hui-Wen, Qin Su-Ping, Li Xiang-Yang, Liu Xiao-Mei, Sun Fen-Fen, Li Hui, Tang Ren-Xian, Zheng Kui-Yang
Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical UniversityXuzhou, Jiangsu Province, China.
Department of Clinical Medicine, Xuzhou Medical UniversityXuzhou, Jiangsu Province, China.
Am J Transl Res. 2017 Sep 15;9(9):4206-4216. eCollection 2017.
This study sought to investigate the anti-inflammatory effect of Polyene Phosphatidylcholine (PPC), a clinical drug that is used to treat hepatopathy, on lipopolysaccharide (LPS)-stimulated macrophages and on bovine collagen II-induced arthritis (CIA) rats. In stimulated primary and Raw264.7 macrophages by LPS, PPC significantly down-regulated the relative expression of mRNA such as IL-6, TNF-α, TLR-2, TLR-4, MyD88, and NF-κB while up-regulated IL-10 and TGF-β expression. Moreover, the concentration of IL-6, TNF-α, IL-10, and TGF-β in the cultured supernatants showed the similar tendency with their mRNA alterations. In addition, PPC could significantly inhibit the LPS-induced expression of MyD88 and NF-κB p65 in both mRNA and protein levels. These results suggest that PPC could down-regulate the LPS-stimulated inflammation in macrophages through TLR-2/TLR-4/MyD88/NF-κB pathway . Furthermore, to explore its effects , PPC was administrated to CIA rats. In comparison to CIA group, PPC-treated rats showed decreased arthritis score and osteopenia. Besides, PPC exhibited its ability to alleviate the degree of synovial hyperplasia, inflammatory cell infiltration, and destruction of cartilage and bone, thus remarkably improving the condition of CIA rats. In short, this study demonstrated that PPC had the potential to be an anti-inflammatory drug to treat inflammatory disorders such as rheumatoid arthritis.
本研究旨在探讨用于治疗肝病的临床药物多烯磷脂酰胆碱(PPC)对脂多糖(LPS)刺激的巨噬细胞和牛胶原蛋白II诱导的关节炎(CIA)大鼠的抗炎作用。在LPS刺激的原代巨噬细胞和Raw264.7巨噬细胞中,PPC显著下调IL-6、TNF-α、TLR-2、TLR-4、MyD88和NF-κB等mRNA的相对表达,同时上调IL-10和TGF-β的表达。此外,培养上清液中IL-6、TNF-α、IL-10和TGF-β的浓度与其mRNA变化呈现相似趋势。此外,PPC在mRNA和蛋白质水平上均能显著抑制LPS诱导的MyD88和NF-κB p65的表达。这些结果表明,PPC可通过TLR-2/TLR-4/MyD88/NF-κB途径下调LPS刺激的巨噬细胞炎症。此外,为探究其作用,将PPC给予CIA大鼠。与CIA组相比,PPC治疗的大鼠关节炎评分降低,骨量减少。此外,PPC表现出减轻滑膜增生、炎性细胞浸润以及软骨和骨破坏程度的能力,从而显著改善CIA大鼠的状况。简而言之,本研究表明PPC有潜力成为治疗类风湿性关节炎等炎症性疾病的抗炎药物。