Deficiency of programmed cell death 4 results in increased IL-10 expression by macrophages and thereby attenuates atherosclerosis in hyperlipidemic mice

• Published in: Cellular & molecular immunology Vol. 13; no. 4; pp. 524 - 534
• Main Authors: Jiang, Yang, Gao, Qi, Wang, Liyang, Guo, Chun, Zhu, Faliang, Wang, Bo, Wang, Qun, Gao, Fei, Chen, Youhai, Zhang, Lining
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2016; Nature Publishing Group
• Subjects: Animals; Antibodies; Antibodies, Neutralizing - pharmacology; Apolipoprotein E; Apolipoproteins E - deficiency; Apoptosis; Apoptosis Regulatory Proteins - deficiency; Apoptosis Regulatory Proteins - metabolism; Arteriosclerosis; Atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - pathology; Biomedical and Life Sciences; Biomedicine; Cell death; Female; High fat diet; Hyperlipidemias - metabolism; Hyperlipidemias - pathology; IL-10; IL-17; Immunology; Inflammatory diseases; Interleukin 10; Interleukin 17; Interleukin-10 - metabolism; Interleukin-17 - metabolism; Lipoproteins, LDL - pharmacology; Lymphocytes T; Macrophages; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - pathology; Male; MAP Kinase Signaling System - drug effects; Medical Microbiology; Mice, Inbred C57BL; Microbiology; Plaque, Atherosclerotic - metabolism; Plaque, Atherosclerotic - pathology; Plaques; Recombinant Proteins - pharmacology; research-article; RNA-Binding Proteins - metabolism; T-Lymphocytes - metabolism; Therapeutic targets; Tumor suppressor genes; Tumors; Vaccine; 动脉粥样硬化; 小鼠; 巨噬细胞; 慢性炎症; 程序性细胞死亡; 高脂血症; atherosclerosis; macrophage; Pdcd4; IL-10
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2015.47

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.