Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury.
Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury.
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急性肺损伤（ALI）是一种严重的疾病，死亡率高且无特异性治疗。最近发现了二十二碳六烯酸衍生介质的保护作用，包括d系列分解蛋白。在这里，我们使用盐酸诱导的小鼠ALI自限模型来确定阿司匹林触发的resolvin D1 （AT-RvD1）对粘膜损伤的影响。RvD1及其受体ALX/FPR2在急性肺损伤小鼠肺组织中得到鉴定。AT-RvD1 （~0.5 ~ 5 μg/kg）可降低炎症峰值，包括支气管肺泡灌洗液（BALF）中性粒细胞约75%。用AT-RvD1治疗的动物上皮和内皮屏障完整性得到改善，气道阻力降低，同时BALF肾上腺素水平升高。AT-RvD1通过下调p -选择素及其配体CD24抑制中性粒细胞-血小板异型相互作用。AT-RvD1还能显著降低BALF促炎因子IL-1β、IL-6、KC、TNF-α水平，降低NF-κB磷酸化的p65核易位。综上所述，这些发现表明AT-RvD1具有有效的粘膜保护作用，并促进ALI后的消退。
Acute Lung Injury (ALI) is a severe illness with excess mortality and no specific therapy. Protective actions were recently uncovered for docosahexaenoic acid -derived mediators, including D-series resolvins. Here, we used a murine self-limited model of hydrochloric acid-induced ALI to determine the effects of aspirin-triggered resolvin D1 (AT-RvD1) on mucosal injury. RvD1 and its receptor ALX/FPR2 were identified in murine lung after ALI. AT-RvD1 (~0.5 – 5 μg/kg) decreased peak inflammation, including bronchoalveolar lavage fluid (BALF) neutrophils by ~75%. Animals treated with AT-RvD1 had improved epithelial and endothelial barrier integrity and decreased airway resistance concomitant with increased BALF epinephrine levels. AT-RvD1 inhibited neutrophil-platelet heterotypic interactions by down-regulating both P-selectin and its ligand CD24. AT-RvD1 also significantly decreased levels of BALF pro-inflammatory cytokines, including IL-1β, IL-6, KC and TNF-α, and decreased NF-κB phosphorylated p65 nuclear translocation. Together, these findings indicate that AT-RvD1 displays potent mucosal protection and promotes catabasis after ALI.
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影响因子：
64.8
作者：
Chiang, Nan;Fredman, Gabrielle;Backhed, Fredrik;Oh, Sungwhan F.;Vickery, Thad;Schmidt, Birgitta A.;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
15.9
作者：
FOLKESSON, HG;MATTHAY, MA;BROADDUS, VC
通讯作者：
BROADDUS, VC
影响因子：
8.8
作者：
Abraham, E
通讯作者：
Abraham, E
影响因子：
30.5
作者：
Haworth, Oliver;Cernadas, Manuela;Levy, Bruce D.
通讯作者：
Levy, Bruce D.
DOI：
10.1161/atvbaha.110.209908
发表时间：
2010-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Fredman G;Van Dyke TE;Serhan CN
通讯作者：
Serhan CN