Immune responsive resolvin D1 programs peritoneal macrophages and cardiac fibroblast phenotypes in diversified metabolic microenvironment.
Immune responsive resolvin D1 programs peritoneal macrophages and cardiac fibroblast phenotypes in diversified metabolic microenvironment.
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DOI：
10.1002/jcp.27165
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发表时间：
2019-04
影响因子：
5.6
通讯作者：
Halade GV
中科院分区：
文献类型：
--
作者：
Kain V;Halade GV
来自n-3和−6脂肪酸的生物活性脂质介体被认为可以调节白细胞。必需脂肪酸向内源性生物活性分子的代谢转化对人类健康起着重要作用。在此，我们测试了底物：亚油酸(LA)和二十二碳六烯酸(DHA)及其生物活性产物；解析素-D_1(RvD_1)和12-S-羟基二十碳四烯酸(HETE)在有或没有脂代谢酶12/15-脂氧合酶(LOX)的情况下调节巨噬细胞可塑性和心脏成纤维细胞表型的潜力。分离野生型(C57BL/6J)和12/15LOX−/−小鼠的腹膜巨噬细胞和心脏成纤维细胞，经DHA、LA、12(S)-HETE、RvD1四种药物作用4、8、12和24小时后，在WT和12/15LOX-α巨噬细胞中(4h)诱导促炎标志物肿瘤坏死因子-β、IL-6、CCL2和IL-1β的表达。生物活性免疫解析剂Rvd1可降低24 h时间点的肿瘤坏死因子-α、IL-6和IL-1β水平。DHA和RvD1均能刺激WT巨噬细胞的Arg-1、Ym-1和MRC-1等前分辨标志物。RvD_1诱导WT_(12/15)LOX−/−巨噬细胞表达Arg-1，即使在12(S)-HETE存在时也是如此。与DHA相比，rvd1在WT和12/15LOX−/−中的表达在24 h时点均达到峰值。与DHA相比，RvD1抑制成纤维细胞中COX-2的表达，但上调5LOX的表达。综上所述，前馈酶与脂肪酸底物和直接介体(Rvd1和12(S)-HETE)的相互作用在确定巨噬细胞表型和心脏成纤维细胞可塑性方面具有响应。特别是，巨噬细胞和成纤维细胞的表型对环境有反应，在有或没有12/15LOX酶的情况下，RvD1调控环境依赖的趋化因子信号来化解炎症。
Bioactive lipid mediators derived from n-3 and −6 fatty acids are known to modulate leukocytes. Metabolic transformation of essential fatty acids to endogenous bioactive molecules plays a major role in human health. Here we tested the potential of substrates; linoleic acid (LA) and docosahexaenoic acid (DHA) and their bioactive products; Resolvin-D1(RvD1) and 12-S-hydroxyeicosatetraenoic acids(HETE) to modulate macrophage plasticity and cardiac fibroblast phenotype in presence or absence of lipid metabolizing enzyme 12/15-lipoxygenase(LOX). Peritoneal macrophages and cardiac fibroblasts were isolated from wild-type (C57BL/6J) and 12/15LOX−/− mice and treated with DHA, LA, 12(S)-HETE), RvD1 for 4,8,12 and 24 h. LA, DHA, 12(S)-HETE and RvD1 elicited mRNA expression of pro-inflammatory markers Tnf-α, IL-6, Ccl2 and IL-1β in WT and in 12/15LOX−/− macrophages at early time-point (4h). Bioactive immunoresolvent RvD1 lowered the levels of Tnf-α, IL-6, and IL-1β at 24 h time-point. Both DHA and RvD1 stimulated the proresolving markers such as Arg-1, Ym-1, and Mrc-1 in WT macrophage. RvD1 induced proresolving phenotype Arg-1 expression in both WT 12/15LOX−/− macrophages even in presence of 12(S)-HETE. RvD1 peaked 5LOX expression in both WT and 12/15LOX−/− at 24 h time-point compared with DHA. RvD1 diminished COX-2 but upregulated 5LOX expression in fibroblast compared with DHA. In summary, the feed-forward enzymatic interaction with fatty acids substrates and direct mediators (RvD1 and 12(S)-HETE) are responsive in determining macrophages phenotype and cardiac fibroblast plasticity. Particularly, macrophages and fibroblast phenotypes are responsive to milieu and RvD1 governs the milieu-dependent chemokine signaling in presence or absence of 12/15LOX enzyme to resolve inflammation.
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影响因子：
3.7
作者：
Hsiao HM;Sapinoro RE;Thatcher TH;Croasdell A;Levy EP;Fulton RA;Olsen KC;Pollock SJ;Serhan CN;Phipps RP;Sime PJ
通讯作者：
Sime PJ
影响因子：
4.4
作者：
Chang CL;Deckelbaum RJ
通讯作者：
Deckelbaum RJ
影响因子：
7.3
作者：
Halade GV;Norris PC;Kain V;Serhan CN;Ingle KA
通讯作者：
Ingle KA
影响因子：
4.4
作者：
Chen, WQ;Esselman, WJ;Busik, JV
通讯作者：
Busik, JV
影响因子：
32.4
作者：
Buckley, Christopher D.;Gilroy, Derek W.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.