The pro-resolving lipid mediator maresin 1 (MaR1) attenuates inflammatory signaling pathways in vascular smooth muscle and endothelial cells.
The pro-resolving lipid mediator maresin 1 (MaR1) attenuates inflammatory signaling pathways in vascular smooth muscle and endothelial cells.
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DOI：
10.1371/journal.pone.0113480
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Conte MS
中科院分区：
文献类型：
--
作者：
Chatterjee A;Sharma A;Chen M;Toy R;Mottola G;Conte MS
炎症及其消退是血管损伤和修复的核心。Maresins包含由二十二碳六烯酸（一种ω-3多不饱和脂肪酸）合成的一个新的生物活性脂质介质家族。已发现它们在巨噬细胞、中性粒细胞和支气管上皮细胞中发挥抗炎和促消退反应，并在腹膜炎和结肠炎的鼠模型中赋予有益作用。我们研究了maresin-1（MaR 1）对肿瘤坏死因子-α（TNF-α）诱导的人血管内皮细胞（EC）和平滑肌细胞（VSMC）炎症反应的影响。采用原代培养的人大隐静脉EC和VSMC。我们测试了天然存在的MaR 1作为TNF-α作用的调节剂，并检查了单核细胞粘附、氧化应激和细胞内炎症信号通路。MaR 1减弱了TNF-α诱导的EC和VSMC中单核细胞粘附和活性氧（ROS）的产生，这与粘附分子E-选择素（EC中）和NADPH氧化酶（NOX 4、NOX 1、NOX 2）的表达（细胞表面）下调有关。MaR 1可抑制TNF-α诱导的EC和VSMC释放促炎介质。MaR 1可减弱TNF-α诱导的NF-κB活化，抑制I-κ激酶（IKK）磷酸化、IκB-α降解和NF- κB p65亚基核转位。MaR 1还可使VSMC和EC内cAMP含量呈时间依赖性增加。MaR 1对EC和VSMC具有广泛的抗炎作用，其机制可能与上调cAMP和下调NF-κB转录因子有关。结果表明，促分解脂质介质MaR 1对血管细胞发挥平衡作用，抵消促炎信号。这些发现可能与急性和慢性血管炎症状态直接相关。
Inflammation and its resolution are central to vascular injury and repair. Maresins comprise a new family of bioactive lipid mediators synthesized from docosahexaenoic acid, an ω-3 polyunsaturated fatty acid. They have been found to exert anti-inflammatory and pro-resolving responses in macrophages, neutrophils and bronchial epithelial cells and impart beneficial actions in murine models of peritonitis and colitis. We investigated the impact of maresin-1 (MaR1) on tumor necrosis factor alpha (TNF-α) induced inflammatory responses in human vascular endothelial (EC) and smooth muscle cells (VSMC). Primary cultures of human saphenous vein EC and VSMC were employed. We tested the naturally occurring MaR1 as modulator of TNF-α effects, with examination of monocyte adhesion, oxidant stress, and intracellular inflammatory signaling pathways. MaR1 attenuated TNF-α induced monocyte adhesion and reactive oxygen species (ROS) generation in both EC and VSMC, associated with down-regulated expression (cell surface) of the adhesion molecule E-selectin (in EC) and NADPH-oxidases (NOX4, NOX1, NOX2). MaR1 attenuated TNF-α induced release of pro-inflammatory mediators by EC and VSMC. MaR1 caused an attenuation of TNF-α induced NF-κB activation in both cell types associated with inhibition of I-κ Kinase (IKK) phosphorylation, IκB-α degradation and nuclear translocation of the NF- κB p65 subunit. MaR1 also caused a time-dependent increase in intracellular cyclic AMP (cAMP) in both naive and TNF-α stimulated VSMC and EC. MaR1 has broad anti-inflammatory actions on EC and VSMC, which may be partly mediated through up-regulation of cAMP and down-regulation of the transcription factor NF-κB. The results suggest that the pro-resolving lipid mediator MaR1 exerts homeostatic actions on vascular cells that counteract pro-inflammatory signals. These findings may have direct relevance for acute and chronic states of vascular inflammation.
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影响因子：
5.8
作者：
Nordgren TM;Heires AJ;Wyatt TA;Poole JA;LeVan TD;Cerutis DR;Romberger DJ
通讯作者：
Romberger DJ
DOI：
10.1111/j.1582-4934.2006.tb00304.x
发表时间：
2006-01
影响因子：
5.3
作者：
Moe KT;Aulia S;Jiang F;Chua YL;Koh TH;Wong MC;Dusting GJ
通讯作者：
Dusting GJ
影响因子：
4.8
作者：
Ollivier, V;Parry, GCN;Mackman, N
通讯作者：
Mackman, N
DOI：
10.1016/j.bbrc.2005.01.089
发表时间：
2005-04-01
影响因子：
3.1
作者：
Goyal, P;Weissmann, N;Hänze, J
通讯作者：
Hänze, J
影响因子：
4.4
作者：
Marcon, Rodrigo;Bento, Allisson F.;Calixto, Joao B.
通讯作者：
Calixto, Joao B.