内源性脂类介质 resolvin E1 来源于二十碳五烯酸，可预防葡聚糖硫酸钠诱导的结肠炎。
Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis.
机构信息
Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
出版信息
Inflamm Bowel Dis. 2010 Jan;16(1):87-95. doi: 10.1002/ibd.21029.
BACKGROUND
Resolvin E1 (RvE1), an endogenous lipid mediator derived from eicosapentaenoic acid, 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 pathogenesis and tissue damage.
METHODS
The RvE1 receptor ChemR23 was expressed in mouse peritoneal macrophages as defined by flow cytometry. Peritoneal macrophages were pretreated with RvE1, followed by lipopolysaccharide stimulation, whereupon transcriptional levels of proinflammatory cytokines were analyzed.
RESULTS
RvE1 treatment led to inhibition of proinflammatory cytokines including TNF-alpha and IL-12p40. In HEK293 cells, pretreatment with RvE1 inhibited TNF-alpha-induced nuclear translocation of NF-kappaB in a ChemR23-dependent manner. These results suggested that RvE1 could regulate proinflammatory responses of macrophages expressing ChemR23. Therefore, we investigated the beneficial effects of RvE1 in dextran sulfate sodium-induced colitis. RvE1 treatment led to amelioration of colonic inflammation.
CONCLUSIONS
These results indicate that RvE1 suppresses proinflammatory responses of macrophages. RvE1 and its receptor may therefore be useful as therapeutic targets in the treatment of human inflammatory bowel disease and other inflammatory disorders.
背景
内源性脂质介质 RvE1（来源于二十碳五烯酸）已在愈合阶段的局部炎症中被鉴定出来。RvE1 可减少几种动物模型中的炎症，包括腹膜炎和视网膜病变，并阻止人中性粒细胞穿过内皮细胞迁移。RvE1 受体 ChemR23 表达在巨噬细胞和树突状细胞等髓样细胞上。本研究旨在确定当巨噬细胞的固有免疫反应在发病机制和组织损伤中起关键作用时，RvE1 是否调节结肠炎症。
方法
通过流式细胞术定义小鼠腹腔巨噬细胞中 RvE1 受体 ChemR23 的表达。用 RvE1 预处理腹腔巨噬细胞，然后用脂多糖刺激，分析前炎症细胞因子的转录水平。
结果
RvE1 处理导致包括 TNF-α和 IL-12p40 在内的前炎症细胞因子的抑制。在 HEK293 细胞中，RvE1 的预处理以 ChemR23 依赖的方式抑制 TNF-α诱导的 NF-κB 核易位。这些结果表明，RvE1 可以调节表达 ChemR23 的巨噬细胞的前炎症反应。因此，我们研究了 RvE1 在葡聚糖硫酸钠诱导的结肠炎中的有益作用。RvE1 处理导致结肠炎症的改善。
结论
这些结果表明 RvE1 抑制巨噬细胞的前炎症反应。因此，RvE1 及其受体可能是治疗人类炎症性肠病和其他炎症性疾病的有用治疗靶点。
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