Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, No.1 Wenyuan Road, Nanjing, 210046, People's Republic of China.
Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Science, Nanjing Normal University, No.1 Wenyuan Road, Nanjing, 210046, Jiangsu, People's Republic of China.
Inflammation. 2020 Jun;43(3):1157-1169. doi: 10.1007/s10753-020-01202-3.
Glutathione S-transferase Pi (GSTP1) was originally identified as one of the cytosolic phase II detoxification enzymes and was also considered to function via its non-catalytic, ligand-binding activity. Autophagy is a self-protective mechanism of the cell to remove unnecessary or dysfunctional components, which plays a crucial role in balancing the beneficial and detrimental effects of immunity and inflammation. However, little is known about whether and how GSTP1 mediates autophagy via inhibiting LPS-induced inflammatory response. Here, we show that LPS-induced autophagy and autophagic flux blockade in THP-1 cells in a concentration- and time-dependent manner. Further, we found that the autophagy activation inhibited the activation of inflammatory signaling pathway and the release of inflammatory factors. However, inhibition of autophagy by 3-methyladenine or chloroquine significantly reduced the anti-inflammatory effect of GSTP1. In addition, our findings provide evidence that GSTP1 regulates autophagy through PI3K-Akt-mTOR pathway and inhibits LPS-induced inflammation. Overall, the current study provides an important reference for future applications of GSTP1 in the treatment of inflammatory diseases.
谷胱甘肽 S-转移酶 Pi（GSTP1）最初被鉴定为细胞溶质 II 期解毒酶之一，并且还被认为通过其非催化、配体结合活性起作用。自噬是细胞清除不必要或功能失调成分的一种自我保护机制，它在平衡免疫和炎症的有益和有害影响方面起着至关重要的作用。然而，人们对于 GSTP1 是否以及如何通过抑制 LPS 诱导的炎症反应来介导自噬知之甚少。在这里，我们表明 LPS 以浓度和时间依赖的方式诱导 THP-1 细胞中的自噬和自噬流阻断。此外，我们发现自噬激活抑制了炎症信号通路的激活和炎症因子的释放。然而，通过 3-甲基腺嘌呤或氯喹抑制自噬会显著降低 GSTP1 的抗炎作用。此外，我们的研究结果提供了证据表明 GSTP1 通过 PI3K-Akt-mTOR 通路调节自噬，并抑制 LPS 诱导的炎症。总的来说，本研究为 GSTP1 在炎症性疾病治疗中的未来应用提供了重要参考。
