Lysophosphatidylinositol (LysoPI), an endogenous ligand for G protein-coupled receptor (GPR) 55, has been known to show various functions in several tissues and cells; however, its roles in the central nervous system (CNS) are not well known. In particular, the detailed effects of LysoPI on microglial inflammatory responses remain unknown. Microglia is the immune cell that has important functions in maintaining immune homeostasis of the CNS. In this study, we explored the effects of LysoPI on inflammatory responses using the mouse microglial cell line BV-2, which was stimulated with lipopolysaccharide (LPS), and some results were confirmed also in rat primary microglia. LysoPI was found to reduce LPS-induced nitric oxide (NO) production and inducible NO synthase protein expression without affecting cell viability in BV-2 cells. LysoPI also suppressed intracellular generation of reactive oxygen species both in BV-2 cells and primary microglia and cytokine release in BV-2 cells. In addition, LysoPI treatment decreased phagocytic activity of LPS-stimulated BV-2 cells and primary microglia. The GPR55 antagonist CID16020046 completely inhibited LysoPI-induced downregulation of phagocytosis in BV-2 microglia, but did not affect the LysoPI-induced decrease in NO production. Our results suggest that LysoPI suppresses microglial phagocytosis via a GPR55-dependent pathway and NO production via a GPR55-independent pathway. LysoPI may contribute to neuroprotection in pathological conditions such as brain injury or neurodegenerative diseases, through its suppressive role in the microglial inflammatory response.

溶血磷脂酰肌醇（LysoPI）是G蛋白偶联受体（GPR）55的内源性配体，在几种组织和细胞中显示出各种功能。然而，其在中枢神经系统（CNS）中的作用尚不为人所知。尤其是，LysoPI对小胶质细胞炎症反应的详细影响仍然未知。小胶质细胞是一种免疫细胞，在维持中枢神经系统的免疫稳态方面具有重要功能。在这项研究中，我们使用脂多糖（LPS）刺激的小鼠小胶质细胞系BV-2探索了LysoPI对炎症反应的影响，并且在大鼠原发性小胶质细胞中也证实了一些结果。发现LysoPI可降低LPS诱导的一氧化氮（NO）产生和可诱导的NO合酶蛋白表达，而不会影响BV-2细胞中的细胞活力。LysoPI还抑制了BV-2细胞和初级小胶质细胞中活性氧物种的细胞内生成以及BV-2细胞中的细胞因子释放。此外，LysoPI处理降低了LPS刺激的BV-2细胞和原发性小胶质细胞的吞噬活性。GPR55拮抗剂CID16020046完全抑制了LysoPI诱导的BV-2小胶质细胞吞噬作用的下调，但不影响LysoPI诱导的NO生成减少。我们的结果表明LysoPI抑制小胶质细胞吞噬作用 GPR55拮抗剂CID16020046完全抑制了LysoPI诱导的BV-2小胶质细胞吞噬作用的下调，但不影响LysoPI诱导的NO生成减少。我们的结果表明，LysoPI抑制小胶质细胞吞噬作用 GPR55拮抗剂CID16020046完全抑制了LysoPI诱导的BV-2小胶质细胞吞噬作用的下调，但不影响LysoPI诱导的NO生成减少。我们的结果表明，LysoPI抑制小胶质细胞吞噬作用经由一个GPR55依赖性途径和NO生产通过一个GPR55-依赖性途径。LysoPI通过在小胶质细胞炎症反应中起抑制作用，可能在诸如脑损伤或神经退行性疾病等病理状况中促进神经保护。