Lysophosphatidylinositols in inflammation and macrophage activation: Altered levels and anti-inflammatory effects
Lysophosphatidylinositols in inflammation and macrophage activation: Altered levels and anti-inflammatory effects
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DOI：
10.1016/j.bbalip.2018.09.003
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发表时间：
2018-12-01
影响因子：
4.8
通讯作者：
Muccioli, Giulio G.
中科院分区：
文献类型：
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作者：
Masquelier, Julien;Alhouayek, Mireille;Muccioli, Giulio G.
溶血磷脂酰肌醇（LPI）是一种生物活性脂质，参与多种病理生理过程，如细胞增殖、迁移和肿瘤发生，并在肥胖和代谢紊乱中发挥作用。通常，LPI的这些作用是由于G蛋白偶联受体GPR 55的激活。然而，LPI和GPR 55在炎症和巨噬细胞活化中的作用仍不清楚。因此，我们想研究巨噬细胞活化和炎症对LPI水平和代谢的影响。为此，我们使用了用脂多糖（LPS，100 ng/mL）活化的培养物中的J774和BV 2细胞以及原代小鼠肺泡和腹膜巨噬细胞。我们还定量了LPI水平在小脑，肺，肝，脾和结肠的小鼠与LPS（300 μ g/kg）诱导的全身炎症和急性结肠炎的小鼠的结肠葡聚糖硫酸钠（DSS）或三硝基苯磺酸（TNBS）和慢性DSS诱导的colis.Our数据表明，LPS诱导的巨噬细胞活化导致改变LPI水平的细胞和培养基。我们还表明，胞质磷脂酶Ala（cPLA 2 α）和α/β-水解酶结构域6（ABHD 6）是在J774巨噬细胞中的LPI代谢中涉及的酶。事实上，ABHD 6和cPLA 2 α抑制增加了LPS激活的巨噬细胞中的20：4-LPI水平。此外，LPS激活的细胞与LPI孵育以GPR 55依赖性方式降低J774活化。在体内，肝脏、脾脏和结肠中的炎症改变了LPI水平。这些变化是组织依赖性的，并可能突出LPI在炎症过程中的潜在作用。
Lysophosphatidylinositols (LPI) are bioactive lipids that are implicated in several pathophysiological processes such as cell proliferation, migration and tumorigenesis and were shown to play a role in obesity and metabolic disorders. Often, these effects of LPI were due to activation of the G protein-coupled receptor GPR55. However, the role of LPI and GPR55 in inflammation and macrophage activation remains unclear. Therefore, we thought to study the effect of macrophage activation and inflammation on LPI levels and metabolism. To do so, we used J774 and BV2 cells in culture activated with lipopolysaccharides (LPS, 100 ng/mL) as well as primary mouse alveolar and peritoneal macrophages. We also quantified LPI levels in the cerebellum, lung, liver, spleen and colon of mice with a systemic inflammation induced by LPS (300 mu g/kg) and in the colon of mice with acute colitis induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) and chronic DSS-induced colitis.Our data show that LPS-induced macrophage activation leads to altered LPI levels in both the cells and culture medium. We also show that cytosolic phospholipase Ala (cPLA2 alpha) and alpha/beta-hydrolase domain 6 (ABHD6) are among the enzymes implicated in LPI metabolism in J774 macrophages. Indeed, ABHD6 and cPLA2 alpha inhibition increased 20:4-LPI levels in LPS-activated macrophages. Furthermore, incubation of LPS-activated cells with LPI decreased J774 activation in a GPR55-dependent manner. In vivo, LPI levels were altered by inflammation in the liver, spleen and colon. These alterations are tissue dependent and could highlight a potential role for LPI in inflammatory processes.