RvD1 ameliorates LPS-induced acute lung injury via the suppression of neutrophil infiltration by reducing CXCL2 expression and release from resident alveolar macrophages
RvD1 ameliorates LPS-induced acute lung injury via the suppression of neutrophil infiltration by reducing CXCL2 expression and release from resident alveolar macrophages
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RvD1 通过减少 CXCL2 表达和驻留肺泡巨噬细胞的释放来抑制中性粒细胞浸润，从而改善 LPS 诱导的急性肺损伤
DOI：
10.1016/j.intimp.2019.105877
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发表时间：
2019
影响因子：
5.6
通讯作者：
Jin Sheng-Wei
中科院分区：
文献类型：
--
作者：
Zhang Hua-Wei;Wang Qian;Mei Hong-Xia;Zheng Sheng-Xing;Abdullahi Mohamed Ali;Wu Qi-Xing;Ye Yang;Xu Hao-Ran;Xiang Shu-Yang;Jin Sheng-Wei
急性肺损伤(ALI)和/或急性呼吸窘迫综合征(ARDS)是威胁生命的危重综合征，其特征是大量炎性细胞的渗透，导致过度的炎症反应。RvD1是一种内源性脂质介质，被认为具有抗炎和促溶解作用。在本研究中，我们研究了RvD1对内毒素(LPS)诱导的ALI小鼠模型的肺炎症反应、中性粒细胞内流和肺损伤的影响。Rvd1对脂多糖诱导的小鼠ALI有保护作用，与未治疗组相比，rvd1治疗组小鼠肺组织病理改变明显减轻，肿瘤坏死因子-α(TN-α)浓度降低，中性粒细胞浸润减少。此外，RvD1通过下调CXCL2在肺泡巨噬细胞上的表达，减轻了内毒素诱导的中性粒细胞的浸润。最后，抑制RvD1受体脂氧素A4受体/甲酰肽受体2(ALX/FPR2)的BOC-2逆转了RvD1的保护作用。这些数据表明，RvD1通过ALX/FPR2依赖的降低肺泡巨噬细胞上CXCL2的表达来抑制中性粒细胞的渗透，从而改善了内毒素诱导的ALI。
Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are life-threatening critical syndromes characterized by the infiltration of a large number of inflammatory cells that lead to an excessive inflammatory response. Resolvin D1 (RvD1), an endogenous lipid mediator, is believed to have anti-inflammatory and proresolving effects. In the present study, we examined the impact of RvD1 on the pulmonary inflammatory response, neutrophil influx, and lung damage in a murine model of lipopolysaccharide (LPS)-induced ALI. Treatment with RvD1 protected mice against LPS-induced ALI, and compared to untreated mice, RvD1-treated mice exhibited significantly ameliorated lung pathological changes, decreased tumor necrosis factor-α (TNF-α) concentrations and attenuated neutrophil infiltration. In addition, treatment with RvD1 attenuated LPS-induced neutrophil infiltration via the downregulation of CXCL2 expression on resident alveolar macrophages. Finally, BOC-2, which inhibits the RvD1 receptor lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2), reversed the protective effects of RvD1. These data demonstrate that RvD1 ameliorates LPS-induced ALI via the suppression of neutrophil infiltration by an ALX/FPR2-dependent reduction in CXCL2 expression on resident alveolar macrophages.