Cordycepin negatively modulates lipopolysaccharide-induced cytokine production by up-regulation of heme oxygenase-1

被引：19

作者：

Qing, Rui ^{[1
]}

Huang, Zezhi ^{[1
]}

Tang, Yufei ^{[1
]}

Xiang, Qingke ^{[1
]}

Yang, Fan ^{[2
]}

机构：

[1] Shaoyang Univ, Dept Lab Med, Div Pathogen Biol, Shaoyang, Peoples R China

[2] Xiangnan Univ, Dept Basic Med, 1 Chengui Rd, Chenzhou 423043, Hunan, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2017年 / 47卷

关键词：

Cordycepin; Heme oxygenase-1; Macrophages; NF-KAPPA-B; INDUCED INFLAMMATION; EXPRESSION; SUPPRESSION; PATHWAY; KINASE; MACROPHAGES; PROTECTS; NRF2;

D O I：

10.1016/j.intimp.2017.03.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Aims: The present study is to investigate the effect of cordycepin on the expression of heme oxygenase-1 (HO-1) in lipopolysaccharide (LPS)-activated microphages, as well as its mechanism of action. Methods: Mouse RAW264.7 cells were treated with different concentrations of cordycepin for 0-16 h. Western blotting was used to determine the expression of HO-1 and the phosphorylation of c-Src and the p47(Phox) subunit of NADPH oxidase. Intracellular reactive oxygen species (ROS) level was determined using H(2)DCFDA as fluorescent probe. Laser-scanning confocal microscopy was used to visualize the nuclear translocation of NF-E2-related factor 2 (Nrf2). Enzyme-linked immunosorbent assay was performed to measure the inhibitory effect of cordycepin on LPS-induced secretion of tumor necrosis factor-alpha and interleukin-6. Results: Cordycepin induced the phosphorylation of c-Src and p47(Phox) subunit of NADPH oxidase in RAW264.7 cells. Cordycepin increased the secretion of ROS by activating NADPH oxidase. In addition, cordycepin enhanced the expression of HO-1 in RAW264.7 cells in both dose-and time-dependent manners. Of note, elevated HO-1 expression induced by cordycepin treatment was regulated by c-Src/NADPH oxidase/ROS pathway. HO-1 expression induced by cordycepin was dependent on the activation of Nrf2, which was regulated by c-Src/NADPH oxidase/ROS. Cordycepin reduced LPS-induced secretion of proinflammatory cytokines through up-regulation of HO-1. Conclusion: The present study demonstrates that cordycepin induces the expression of HO-1 in RAW264.7 cells via c-Src/NADPH oxidase/ROS/Nrf2 pathway, and plays an anti-inflammatory role by inhibiting the secretion of cytokines from macrophages. (C) 2017 Elsevier B.V. All rights reserved.

引用

页码：20 / 27

页数：8

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