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首页> 外文期刊>Journal of Cellular Physiology >Epoxyeicosatrienoic Acids Regulate Macrophage Polarization and Prevent LPS-Induced Cardiac Dysfunction
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Epoxyeicosatrienoic Acids Regulate Macrophage Polarization and Prevent LPS-Induced Cardiac Dysfunction

机译:Epoxyeicosatrienoic酸调节巨噬细胞极化,防止LPS-Induced心脏功能障碍

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Macrophages, owning tremendous phenotypic plasticity and diverse functions, were becoming the target cells in various inflammatory, metabolic and immune diseases. Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to form epoxyeicosatrienoic acids (EETs), which possess various beneficial effects on cardiovascular system. In the present study, we evaluated the effects of EETs treatment on macrophage polarization and recombinant adeno-associated virus (rAAV)-mediated CYP2J2 expression on lipopolysaccharide (LPS)-induced cardiac dysfunction, and sought to investigate the underlying mechanisms. In vitro studies showed that EETs (1 mu mol/L) significantly inhibited LPS-induced M1 macrophage polarization and diminished the proinflammatory cytokines at transcriptional and post-transcriptional level; meanwhile it preserved M2 macrophage related molecules expression and upregulated anti-inflammatory cytokine IL-10. Furthermore, EETs down-regulated NF-B activation and up-regulated peroxisome proliferator-activated receptors (PPAR/) and heme oxygenase 1 (HO-1) expression, which play important roles in regulating M1 and M2 polarization. In addition, LPS treatment in mice induced cardiac dysfunction, heart tissue damage and infiltration of M1 macrophages, as well as the increase of inflammatory cytokines in serum and heart tissue, but rAAV-mediated CYP2J2 expression increased EETs generation in heart and significantly attenuated the LPS-induced harmful effects, which mechanisms were similar as the in vitro study. Taken together, the results indicate that CYP2J2/EETs regulates macrophage polarization by attenuating NF-B signaling pathway via PPAR/ and HO-1 activation and its potential use in treatment of inflammatory diseases. J. Cell. Physiol. 230: 2108-2119, 2015. (c) 2015 Wiley Periodicals, Inc.
机译:巨噬细胞,拥有巨大的表型可塑性和多样化的功能,成为靶细胞的各种炎症,代谢和免疫疾病。epoxygenase 2 j2 (CYP2J2)代谢花生四烯酸酸形成epoxyeicosatrienoic酸(缺钱),拥有各种有益吗心血管系统。邂逅了治疗的效果进行评估巨噬细胞极化和重组腺相关病毒(rAAV)介导CYP2J2表达对脂多糖(LPS)全身心脏功能障碍,并试图调查底层机制。表明,特点显著(1μmol / L)抑制LPS-induced M1巨噬细胞极化和减少促炎细胞因子转录和转录后水平;与此同时它保存M2巨噬细胞相关分子表达和调节抗炎细胞因子il - 10。邂逅了抑制NF-B激活和差异过氧物酶体proliferator-activated受体(PPAR)和血红素加氧酶1 (HO-1)表达式,它扮演了一个重要的角色调节M1和M2极化。有限合伙人治疗心脏诱发小鼠功能障碍,心脏组织损伤和渗透M1的巨噬细胞,以及增加血清中炎性细胞因子和心脏组织,但rAAV-mediated CYP2J2表达增加邂逅了一代在心脏和显著减毒LPS-induced有害影响,机制是类似的体外研究。总的来说,结果表明,CYP2J2 /特点调节巨噬细胞极化通过PPAR /和衰减NF-B信号通路HO-1激活和其潜在的使用炎症性疾病的治疗。杂志。230:2108 - 2119年,2015年。期刊、公司。

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