标题:Deficiency of programmed cell death 4 results in increased IL-10 expression by macrophages and thereby attenuates atherosclerosis in hyperlipidemic mice
作者:Jiang, Yang; Gao, Qi; Wang, Liyang; Guo, Chun; Zhu, Faliang; Wang, Bo; Wang, Qun; Gao, Fei; Chen, Youhai; Zhang, Lining
作者机构:[Jiang Yang] Department of Immunology, School of Medicine, Shandong University, Jinan, Shandong China.;[Gao Qi] Department of Immunology, School of Me 更多
通讯作者:Zhang, L(zhanglining@sdu.edu.cn)
通讯作者地址:[Zhang, LN]Shandong Univ, Sch Med, Dept Immunol, 44 Wen Hua Western Rd, Jinan 250012, Shandong, Peoples R China.
来源:细胞分子免疫学
出版年:2016
卷:13
期:4
页码:524-534
DOI:10.1038/cmi.2015.47
关键词:atherosclerosis; IL-10; macrophage; Pdcd4
摘要:Programmed cell death 4 (Pdcd4) is a newly defined inhibitor of transcription and translation and a tumor suppressor. Recent studies have suggested that Pdcd4 may also be involved in some inflammatory diseases. However, its role in atherosclerosis, a chronic inflammation of the arterial wall, remains to be investigated. Here, we found that Pdcd4 deficiency in mice increased the expression of IL-10 in macrophages and decreased the expression of IL-17 in T cells in the presence of an atherosclerosis-associated stimulator in vitro and in high fat-induced atherosclerotic plaques. Importantly, knocking out Pdcd4 led to a decrease in atherosclerotic lesions in Apoe(-/-) mice fed a high fat diet. This effect could be partly reversed by blocking IL-10 with a neutralizing antibody but not by the application of exogenous IL-17. Further mechanistic studies revealed that Pdcd4 negatively regulated the expression of IL-10 in an ERK1/2-and p38-dependent manner. These results demonstrate that Pdcd4 deficiency attenuates atherosclerosis in hyperlipidemic mice in part through the upregulation of the anti-inflammatory cytokine IL-10. This indicates that endogenous Pdcd4 promotes atherosclerosis and therefore represents a potential therapeutic target for patients with atherosclerosis.
收录类别:CSCD;SCOPUS;SCIE
WOS核心被引频次:9
Scopus被引频次:11
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84977495034&doi=10.1038%2fcmi.2015.47&partnerID=40&md5=47c03ddfb6f9e2d196baa131ae72d3e7
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