LRP1 receptor-mediated immunosuppression of α-MMC on monocytes

被引：16

作者：

Deng, Nianhua ^{[1
]}

Li, Minhui ^{[2
]}

Shen, Dai ^{[3
]}

He, Qianchuan ^{[4
]}

Sun, Wenkui ^{[1
]}

Liu, Mengling ^{[5
]}

Liu, Yang ^{[6
]}

Zhou, Yiping ^{[1
]}

Zheng, Juecun ^{[1
]}

Shen, Fubing ^{[1
]}

机构：

[1] Chengdu Med Coll, Sch Lab Med, Chengdu 610500, Sichuan, Peoples R China

[2] Chengdu Med Coll, Ctr Sci & Res, Chengdu 610500, Sichuan, Peoples R China

[3] Chengdu Fudai Biol Med Co Ltd, Chengdu 610213, Sichuan, Peoples R China

[4] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA

[5] Chengdu Med Coll, Sch Pharm, Chengdu 610500, Sichuan, Peoples R China

[6] Wright State Univ, Dept Math & Stat, Dayton, OH 45435 USA

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2019年 / 70卷

基金：

中国国家自然科学基金;

关键词：

Alpha-MMC; Immunosuppression; Cytokine; LRP1; MAPK; MOMORDICA-CHARANTIA; CHEMOKINE RANTES; MAP KINASE; PROTEIN; PROGRESSION; EXPRESSION; CELLS; MACROPHAGES; ACTIVATION; MECHANISM;

D O I：

10.1016/j.intimp.2019.01.036

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Alpha-MMC is a type I ribosome-inactivating protein purified from bitter gourd that has strong anti-tumour and antiviral activity. Alpha-MMC also has immunosuppressive effects, but the mechanism of these immunosuppressive effects remains unclear. It is reported that the binding of alpha-MMC to its specific cell membrane LRP1 receptor is key to its biological effects. In this study, we investigated the effect of alpha-MMC on cytotoxicity and cytokine release regulation in three immune cells, human monocyte THP-1 cells, B-lymphocyte WIL2 cells and T-lymphocyte H9 cells, and explored the correlation between this effect and LRP1 receptor distribution on these three cell types. We demonstrate that alpha-MMC has a significant effect of apoptosis induction and cytokine release in THP-1 cells but has no effect on WIL2-S and H9 cells. Specifically, at a non-cytotoxic dose (80 mu g/ml), alpha-MMC regulates THP-1 cells by inhibiting IL-1 beta, IL-2, IL-8, IL-9, IL-12, MIP-1 alpha/beta, MCP-1 and TNF-alpha expression and enhancing IL-1ra and RANTES expression, resulting in the inhibition of cellular immune function. Subsequent experiments showed that the cytokine expression regulated by alpha-MMC can be blocked by silencing the LRP1 receptor of alpha-MMC. Further research indicated that phosphorylation of 9 signalling proteins of the MAPK pathway was significantly regulated by alpha-MMC and was blocked by LRP1 silencing. We conclude that the regulation of cytokine expression induced by alpha-MMC in monocyte THP-1 cells is mediated by the LRP1 receptor, likely via the MAPK signalling pathway. Our results suggest that the inhibition effect on monocytes/macrophages mediates the immunosuppressive function of alpha-MMC. Due to the selective cytotoxicity and cytokine release regulation of alpha-MMC in monocytes/macrophages, alpha-MMC may be used for killing Tumour-Associated Macrophages (M2 subtypes) or inhibiting their cytokine release in the tumour microenvironment.

引用

页码：80 / 87

页数：8

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