炎症
巨噬细胞
造血
促炎细胞因子
骨髓
细胞因子
泡沫电池
免疫学
免疫系统
生物
M2巨噬细胞
干细胞
细胞生物学
体外
生物化学
作者
Sara McCurdy,Yvonne Baumer,Emma Toulmin,Bog‐Hieu Lee,William A. Boisvert
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2017-10-14
卷期号:199 (10): 3604-3613
被引量:32
标识
DOI:10.4049/jimmunol.1601907
摘要
Abstract Atherosclerosis, the progressive buildup of plaque within arterial blood vessels, can lead to fatal downstream events, such as heart attack or stroke. A key event contributing to the development of atherosclerosis is the infiltration of monocytes and its associated inflammation, as well as the formation of lipid-laden macrophage foam cells within the vessel wall. IL-37 is recognized as an important anti-inflammatory cytokine expressed especially by immune cells. This study was undertaken to elucidate the role of macrophage-expressed IL-37 in reducing the production and effects of proinflammatory cytokines, preventing foam cell formation, and reducing the development of atherosclerosis. Expression of human IL-37 was achieved with a macrophage-specific overexpression system, using the CD68 promoter in mouse primary bone marrow–derived macrophages via retroviral transduction. Macrophage IL-37 expression in vitro resulted in decreased mRNA (e.g., IL-1B, IL-6, and IL-12) and secreted protein production (e.g., IL-6, M-CSF, and ICAM-1) of key inflammatory mediators. IL-37 expression also inhibited macrophage proliferation, apoptosis, and transmigration, as well as reduced lipid uptake, compared with controls in vitro. The in vivo effects of macrophage-expressed IL-37 were investigated through bone marrow transplantation of transduced hematopoietic stem cells into irradiated atherosclerosis-prone Ldlr−/− mice. After 10 wk on a high-fat/high-cholesterol diet, mice with IL-37–expressing macrophages showed reduced disease pathogenesis, which was demonstrated by significantly less arterial plaque development and systemic inflammation compared with control mice. The athero-protective effect of macrophage-expressed IL-37 has implications for development of future therapies to treat atherosclerosis, as well as other chronic inflammatory diseases.
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