Lactate Inhibits the Pro-Inflammatory Response and Metabolic Reprogramming in Murine Macrophages in a GPR81-Independent Manner.
Lactate Inhibits the Pro-Inflammatory Response and Metabolic Reprogramming in Murine Macrophages in a GPR81-Independent Manner.
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DOI：
10.1371/journal.pone.0163694
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Rumbo M
中科院分区：
文献类型：
--
作者：
Errea A;Cayet D;Marchetti P;Tang C;Kluza J;Offermanns S;Sirard JC;Rumbo M
乳酸是哺乳动物碳代谢的重要组成部分。最近，乳酸被证明通过G蛋白偶联受体81(GPR81)发出信号，从而调节炎症过程。这项研究表明，乳酸以一种不依赖GPR81的方式抑制促炎信号。脂多糖(LPS)刺激骨髓巨噬细胞表达IL-6、IL-12p40和CD40的同时，乳酸能剂量依赖性地阻断Gpr81-/-细胞和野生型细胞的这些反应。当糖酵解被化学抑制剂阻断时，巨噬细胞的激活受到损害。值得注意的是，乳酸在野生型和Gpr81-/-细胞中被发现抑制了内毒素诱导的糖酵解。总之，我们的研究表明，乳酸可以诱导GPR81非依赖性的代谢变化，调节巨噬细胞的促炎激活。
Lactate is an essential component of carbon metabolism in mammals. Recently, lactate was shown to signal through the G protein coupled receptor 81 (GPR81) and to thus modulate inflammatory processes. This study demonstrates that lactate inhibits pro-inflammatory signaling in a GPR81-independent fashion. While lipopolysaccharide (LPS) triggered expression of IL-6 and IL-12 p40, and CD40 in bone marrow-derived macrophages, lactate was able to abrogate these responses in a dose dependent manner in Gpr81-/- cells as well as in wild type cells. Macrophage activation was impaired when glycolysis was blocked by chemical inhibitors. Remarkably, lactate was found to inhibit LPS-induced glycolysis in wild type as well as in Gpr81-/- cells. In conclusion, our study suggests that lactate can induce GPR81-independent metabolic changes that modulate macrophage pro-inflammatory activation.
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影响因子：
44.1
作者：
通讯作者：
--
影响因子：
7.2
作者：
Nasi A;Rethi B
通讯作者：
Rethi B
DOI：
10.1038/nri3771
发表时间：
2015-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
O'Hanlon DE;Moench TR;Cone RA
通讯作者：
Cone RA
影响因子：
11.2
作者：
Doherty JR;Yang C;Scott KE;Cameron MD;Fallahi M;Li W;Hall MA;Amelio AL;Mishra JK;Li F;Tortosa M;Genau HM;Rounbehler RJ;Lu Y;Dang CV;Kumar KG;Butler AA;Bannister TD;Hooper AT;Unsal-Kacmaz K;Roush WR;Cleveland JL
通讯作者：
Cleveland JL