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Arctigenin Ameliorates Inflammation by Regulating Accumulation and Functional Activity of MDSCs in Endotoxin Shock

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Abstract

Endotoxin shock is a life-threatening response caused by a disordered immune response to an infection. MDSCs are accumulated and play a protective role in the pathogenesis of endotoxin shock. However, the regulation of MDSCs by small molecule remains unrevealed. Here, we report that arctigenin, a small molecule extracted from Arctium lappa, induces accumulation of functional MDSCs. Arctigenin was able to ameliorate LPS-induced inflammation through accumulating MDSCs, especially granulocytic MDSCs (G-MDSCs), and enhancing the immunosuppressive function of MDSCs in vivo and in vitro. Mechanistically, arctigenin promoted the accumulation of MDSCs through upregulating miR-127-5p which targets the 3′UTR of interferon regulatory factor-8 (IRF8) mRNA. In addition, arctigenin enhanced the immunosuppressive activity of MDSCs on M1 macrophage polarization by elevating the expression of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS). Our study provides new insights into the regulation of functional MDSCs by arctigenin in exerting immune responses and pathogenesis of inflammatory diseases.

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Funding

This study was funded by the Shandong Provincial Natural Science Foundation, China (No. ZR2017BH057, No. ZR2017BH016); Projects of Science and Technology in Shandong Province, China (No. J17KA230); and Projects of Jining Medical University (JY2017KJ009).

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Authors and Affiliations

  1. Institute of Immunology and Molecular Medicine, Jining Medical University, Shandong, 272067, China

    Hui Shi, Guanjun Dong, Fenglian Yan, Hui Zhang, Chunxia Li, Qun Ma, Junfeng Zhang, Zhaochen Ning, Zhihua Li, Jun Dai, Jiankuo Ming, Chuanping Si & Huabao Xiong

  2. State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin, 300071, People’s Republic of China

    Runping Fang

  3. Department of Medicine, Icahn School of Medicine at Mount Sinai, Immunology Institute, New York, NY, 10029, USA

    Huabao Xiong

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  1. Hui Shi
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Correspondence to Huabao Xiong.

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The research was approved by the Jining University Institution Animal Care and Use Committee.

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Shi, H., Dong, G., Yan, F. et al. Arctigenin Ameliorates Inflammation by Regulating Accumulation and Functional Activity of MDSCs in Endotoxin Shock. Inflammation 41, 2090–2100 (2018). https://doi.org/10.1007/s10753-018-0852-1

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