Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis.
Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis.
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DOI：
10.1002/ibd.21029
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发表时间：
2010-01
影响因子：
4.9
通讯作者：
Azuma, Takeshi
中科院分区：
文献类型：
--
作者：
Ishida, Tsukasa;Yoshida, Masaru;Arita, Makoto;Nishitani, Yosuke;Nishiumi, Shin;Masuda, Atsuhiro;Mizuno, Shigeto;Takagawa, Tetsuya;Morita, Yoshinori;Kutsumi, Hiromu;Inokuchi, Hideto;Serhan, Charles N.;Blumberg, Richard S.;Azuma, Takeshi
Resolvin E1 （RvE1）是一种来源于二十碳五烯酸（EPA）的内源性脂质介质，已经在愈合阶段的局部炎症中被发现。RvE1在几种动物模型中减轻炎症，包括腹膜炎和视网膜病变，并阻断人类中性粒细胞跨内皮细胞迁移。RvE1受体ChemR23在骨髓细胞如巨噬细胞和树突状细胞上表达。本研究的目的是确定当巨噬细胞的先天免疫反应在其发病机制和组织损伤中起关键作用时，RvE1是否调控结肠炎症。通过流式细胞术检测，RvE1受体ChemR23在小鼠腹腔巨噬细胞中表达。用RvE1预处理腹腔巨噬细胞，然后用脂多糖（LPS）刺激，分析促炎细胞因子的转录水平。RvE1治疗导致促炎细胞因子包括TNF-α和IL-12p40的抑制。在HEK293细胞中，RvE1预处理以依赖于ChemR23的方式抑制TNF-α-诱导的NF-κB核易位。这些结果表明，RvE1可以调节表达ChemR23的巨噬细胞的促炎反应。因此，我们研究了RvE1在葡聚糖硫酸钠（DSS）诱导的结肠炎中的有益作用。RvE1治疗可改善结肠炎症。这些结果表明RvE1抑制巨噬细胞的促炎反应。因此，RvE1及其受体可能是治疗人类炎症性肠病（IBD）和其他炎症性疾病的有效靶点。
Resolvin E1 (RvE1), an endogenous lipid mediator derived from eicosapentaenoic acid (EPA), has been identified in local inflammation during the healing stage. RvE1 reduces inflammation in several types of animal models including peritonitis and retinopathy, and blocks human neutrophil transendothelial cell migration. The RvE1 receptor ChemR23 is expressed on myeloid cells such as macrophages and dendritic cells. The aim of this study was to determine whether RvE1 regulates colonic inflammation when the innate immune response of macrophages plays a key role in the pathogenesis and tissue damage. RvE1 receptor, ChemR23, was expressed in mouse peritoneal macrophages as defined by flow cytometry. Peritoneal macrophages were pretreated with RvE1, followed by lipopolysaccharide (LPS) stimulation whereupon of the transcriptional levels of proinflammatory cytokines were analyzed. RvE1 treatment led to the inhibition of proinflammatory cytokines including TNF-α and IL-12p40. In HEK293 cells, pretreatment with RvE1 inhibited TNF-α-induced nuclear translocation of NF-κB in a ChemR23 dependent manner. These results suggested that RvE1 could regulate pro-inflammatory responses of macrophages expressing ChemR23. Therefore, we investigated the beneficial effects of RvE1 in dextran sulfate sodium (DSS) induced colitis. RvE1 treatment led to amelioration of colonic inflammation. These results indicate that RvE1 suppresses pro-inflammatory responses of macrophages. RvE1 and its receptor may therefore be useful as therapeutic targets in the treatment of human inflammatory bowel disease (IBD) and other inflammatory disorders.
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DOI：
10.1084/jem.192.8.1197
发表时间：
2000-10-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Serhan CN;Clish CB;Brannon J;Colgan SP;Chiang N;Gronert K
通讯作者：
Gronert K
影响因子：
3.7
作者：
Haas-Stapleton, Eric J.;Lu, Yan;Agabian, Nina
通讯作者：
Agabian, Nina
影响因子：
4.9
作者：
Hanauer, SB
通讯作者：
Hanauer, SB
影响因子：
3.8
作者：
Overbergh, L;Valckx, D;Mathieu, C
通讯作者：
Mathieu, C
影响因子：
4.4
作者：
Hasturk, Hatice;Kantarci, Alpdogan;Van Dyke, Thomas E.
通讯作者：
Van Dyke, Thomas E.