Shibaike Yuki, Gotoh Mari, Ogawa Chinatsu, Nakajima Shingo, Yoshikawa Keisuke, Kobayashi Tetsuyuki, Murakami-Murofushi Kimiko
Endowed Research Division of Beauty and Science, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan.
Research Organization for the Promotion of Global Women's Leadership, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan.
Biochem Biophys Rep. 2019 Jul 19;19:100668. doi: 10.1016/j.bbrep.2019.100668. eCollection 2019 Sep.
Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator that contains a unique cyclic phosphate ring at the -2 and -3 positions of its glycerol backbone. Using mouse models for multiple sclerosis (cuprizone-induced demyelination and experimental autoimmune encephalomyelitis) and traumatic brain injury, we revealed that cPA and its metabolically stabilized cPA derivative, 2-carba-cPA (2ccPA), have potential to protect against neuroinflammation. In this study, we investigated whether 2ccPA has anti-inflammatory effect on peripheral immune function or not using inflammation-induced macrophages-like cell line, THP-1 monocytes differentiated by phorbol 12-myristate 13-acetate (PMA). Lipopolysaccharide (LPS)-stimulated THP-1 cells were found to have higher expression of the mRNAs of several inflammation-related cytokines and of the enzyme cyclooxygenase-2 (Cox-2); however, when THP-1 cells were stimulated by LPS in the presence of 2ccPA, the increase in the expression of pro-inflammatory cytokine and Cox-2 mRNA was attenuated. 2ccPA treatment also decreased the amount of prostaglandin E2 (PGE2) produced by LPS-stimulated THP-1 cells and decreased expression of the mRNA of prostaglandin E receptor 2 (EP2, ), a PGE2 receptor that mediates inflammation. These results indicate that 2ccPA has anti-inflammatory properties.
环磷酸腺苷（cPA）是一种天然存在的磷脂介质，在其甘油主链的-2和-3位含有独特的环磷酸环。利用多发性硬化症（铜离子螯合剂诱导的脱髓鞘和实验性自身免疫性脑脊髓炎）和创伤性脑损伤的小鼠模型，我们发现cPA及其代谢稳定的cPA衍生物2-碳-cPA（2ccPA）具有预防神经炎症的潜力。在本研究中，我们使用炎症诱导的巨噬细胞样细胞系、经佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）分化的THP-1单核细胞，研究了2ccPA是否对外周免疫功能具有抗炎作用。发现脂多糖（LPS）刺激的THP-1细胞中几种炎症相关细胞因子的mRNA以及环氧合酶-2（Cox-2）的表达较高；然而，当THP-1细胞在2ccPA存在的情况下受到LPS刺激时，促炎细胞因子和Cox-2 mRNA的表达增加受到抑制。2ccPA处理还降低了LPS刺激的THP-1细胞产生的前列腺素E2（PGE2）的量，并降低了前列腺素E受体2（EP2）的mRNA表达，EP2是一种介导炎症的PGE2受体。这些结果表明2ccPA具有抗炎特性。
