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GSTP1 Inhibits LPS-Induced Inflammatory Response Through Regulating Autophagy in THP-1 Cells

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Abstract

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.

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Acknowledgments

This work was financially supported by grants from the Natural Science Foundation of China (Nos. 81671565, 81771703 and 31571166), the Priority Academic Program Development of Jiangsu Higher Education Institution (PADD).

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  1. Xiaowen Bi and Jinfei Li contributed equally to this work.

Authors and Affiliations

  1. 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

    Xiaowen Bi, Jinfei Li, XiRui Fan, Jinyi Zhou, Baolin Jiang & Zhimin Yin

  2. 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

    Zhou Yang

  3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, People’s Republic of China

    Lan Luo

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  1. Xiaowen Bi
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Contributions

Conceived and designed the experiments: Z. Yin, L. Luo, Z. Yang, J. Li and X. Bi. Performed the experiments: X. Bi, J. Li, X. Fan, J. Zhou, B. Jiang. Analyzed the data: X. Bi, J. Li and Z. Yin. Wrote the paper: X. Bi and Z. Yin.

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Correspondence to Zhou Yang, Lan Luo or Zhimin Yin.

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Bi, X., Li, J., Fan, X. et al. GSTP1 Inhibits LPS-Induced Inflammatory Response Through Regulating Autophagy in THP-1 Cells. Inflammation 43, 1157–1169 (2020). https://doi.org/10.1007/s10753-020-01202-3

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