RvD1 accelerates the resolution of inflammation by promoting apoptosis of the recruited macrophages via the ALX/FasL-FasR/caspase-3 signaling pathway.
RvD1 accelerates the resolution of inflammation by promoting apoptosis of the recruited macrophages via the ALX/FasL-FasR/caspase-3 signaling pathway.
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DOI：
10.1038/s41420-021-00708-5
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发表时间：
2021-11-08
影响因子：
7
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Xiang SY;Ye Y;Yang Q;Xu HR;Shen CX;Ma MQ;Jin SW;Mei HX;Zheng SX;Smith FG;Jin SW;Wang Q
炎症分解障碍引起的炎症反应失控是急性呼吸窘迫综合征(ARDS)的原因之一。当炎性单核细胞，即被称为招募巨噬细胞，从循环迁移到肺时，巨噬细胞池显著扩大。募集的巨噬细胞的持续存在导致炎症消退阶段的慢性炎症。相反，清除损伤部位募集的巨噬细胞会导致炎症迅速消退。RvD1是一种来源于二十二碳六烯酸的内源性脂质介质。小鼠在内毒素刺激后第3天和第4天经尾静脉注射RvD1。RvD1可降低肺组织炎症因子水平，促进抗炎M2表型，增强巨噬细胞吞噬功能，减轻急性肺损伤。经RvD1处理后，BAL液中巨噬细胞数明显减少。RvD1可部分通过FasL-Fasr/caspase-3信号通路促进巨噬细胞的凋亡，此作用可被ALX/PRP2抑制剂Boc-2阻断。综上所述，我们的发现强化了治疗靶向导致招募的巨噬细胞凋亡的概念。因此，RvD1可能为ARDS的解决提供一种新的治疗方法。
The uncontrolled inflammatory response caused by a disorder in inflammation resolution is one of the reasons for acute respiratory distress syndrome (ARDS). The macrophage pool markedly expands when inflammatory monocytes, known as recruited macrophages, migrate from the circulation to the lung. The persistent presence of recruited macrophages leads to chronic inflammation in the resolution phase of inflammation. On the contrary, elimination of the recruited macrophages at the injury site leads to the rapid resolution of inflammation. Resolvin D1 (RvD1) is an endogenous lipid mediator derived from docosahexaenoic acid. Mice were administered RvD1 via the tail vein 3 and 4 days after stimulation with lipopolysaccharide. RvD1 reduced the levels of the inflammatory factors in the lung tissue, promoted the anti-inflammatory M2 phenotype, and enhanced the phagocytic function of recruited macrophages to alleviate acute lung injury. We also found that the number of macrophages was decreased in BAL fluid after treatment with RvD1. RvD1 increased the apoptosis of recruited macrophages partly via the FasL-FasR/caspase-3 signaling pathway, and this effect could be blocked by Boc-2, an ALX/PRP2 inhibitor. Taken together, our findings reinforce the concept of therapeutic targeting leading to the apoptosis of recruited macrophages. Thus, RvD1 may provide a new therapy for the resolution of ARDS.
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影响因子：
30.5
作者：
Aegerter, Helena;Kulikauskaite, Justina;Wack, Andreas
通讯作者：
Wack, Andreas
影响因子：
81.5
作者：
Matthay, Michael A.;Zemans, Rachel L.;Calfee, Carolyn S.
通讯作者：
Calfee, Carolyn S.
影响因子：
46.9
作者：
Thepen, T;van Vuuren, AJH;van de Winkel, JGJ
通讯作者：
van de Winkel, JGJ
DOI：
10.1073/pnas.1206641109
发表时间：
2012-09-11
影响因子：
11.1
作者：
El Kebir, Driss;Gjorstrup, Per;Filep, Janos G.
通讯作者：
Filep, Janos G.
专门的促解决介质：感染和炎症的内源性调节剂。
DOI：
10.1038/nri.2015.4
发表时间：
2016-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Basil MC;Levy BD
通讯作者：
Levy BD