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Discovery of a polysaccharide from the fruiting bodies of Lepista sordida as potent inhibitors of indoleamine 2, 3-dioxygenase (IDO) in HepG2 cells via blocking of STAT1-mediated JAK-PKC-delta signaling pathways

文献类型： 外文期刊

作者： Luo, Qiang 1 ; Yan, Liang 2 ; Xu, Pan 1 ; Xiong, Chuan 4 ; Yang, Zhirong 5 ; Hu, Peng 1 ; Hu, Huidong 1 ; Hong, Ren 1 ;

作者机构： 1.Chongqing Med Univ, Key Lab Mol Biol Infect Dis, Affiliated Hosp 2,Inst Viral Hepatitis, Chinese Minist Educ,Dept Infect Dis, Chongqing 400010, Peoples R China

2.Chongqing Med Univ, Childrens Hosp, Pediat Res Inst, Minist Educ,Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China

3.China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China

4.Sichuan Acad Agr Sci, Biotechnol & Nucl Technol Res Inst, Chengdu 610061, Sichuan, Peoples R China

5.Sichuan Univ, Coll Life Sci, Sichuan Prov Key Lab Nat Resources Microbiol & Te, Chengdu 610064, Sichuan, Peoples R China

关键词： Hepatocellular carcinoma (HCC); Indoleamine 2,3-dioxygenase (IDO); Lepista sordid polysaccharide; JAK-PKC-delta-STAT1 signaling pathway; IFN-gamma

期刊名称：CARBOHYDRATE POLYMERS （ 影响因子：9.381； 五年影响因子：8.678 ）

ISSN： 0144-8617

年卷期： 2018 年 197 卷

页码：

收录情况： SCI

摘要： The present study examined the role of a polysaccharide (LSP, 25 and 100 mu g/ml) from the fruiting bodies of Lepista sordid on the immunosuppressive enzyme indoleamine 2, 3-dioxygenase (IDO) in HepG2 cells, and the possible mechanism of action. IDO expression and kynurenine production from LSP-treated HepG2 cells following IFN-gamma stimulation were dramatically inhibited by LSP treatment. In line with this, the medium of HepG2 cells pretreated with LSP improved the survival rate of primary CD4+ and CD8+ T cells as compared with IFN-gamma-ctreated control cells. Moreover, tyrosine 701 and serine 727 phosphorylation of STAT1 were dramatically reduced by LSP pretreatment in IFN-gamma-stimulated HepG2 cells. Furthermore phosphorylation of JAK-1 and JAK-2 was also inhibited by LSP. Additionally, two IDO promoters (GAS and ISRE) were inhibited in cells pretreated with LSP prior to IFN-gamma exposure. These findings suggest that LSP exerts antitumor effects on HepG2 cells by inhibiting IDO via JAK-PKC-delta-STAT1 signaling pathway.

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