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
通讯作者地址：[Zhang, LN]Shandong Univ, Sch Med, Dept Immunol, 44 Wen Hua Western Rd, Jinan 250012, Shandong, Peoples R China.
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.