Resolvin D4 mitigates lipopolysaccharide-induced lung injury in mice

IF 3
Rika Inomata , Hironobu Tsubouchi , Toshifumi Takao , Mone Kurokawa , Shigehisa Yanagi , Katsuya Sakai , Taiga Miyazaki
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引用次数: 0

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening condition involving severe lung inflammation. The excessive oxidative stress and persistent inflammation that occur in ARDS lead to decreased epithelial integrity and hypoxemia due to pulmonary edema via increased vascular permeability. Resolvin D4 (RvD4) is one of the lipid mediators that is biosynthesized from omega-3 polyunsaturated fatty acids. It plays a role in the resolution of inflammation and reduces oxidative stress and cell death. We investigated the therapeutic potential of the administration of RvD4 in a murine model of lipopolysaccharide (LPS)-induced ARDS. Concurrent with the intratracheal administration of LPS, RvD4 or saline was administered to mice via the caudal vein every 12 h. This treatment with RvD4 alleviated the LPS-induced infiltration of inflammatory cells in lungs, inhibited increased pulmonary vascular permeability, decreased the levels of IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF), and suppressed the reduction of the expression levels of the tight junction protein, Zonula occludens-1 (Zo-1) and the NAD+-dependent deacetylase, Sirtuin-3 (Sirt3). In vitro experiments revealed that in LPS-stimulated BEAS-2B cells, treatment with RvD4 suppressed the increases in the expressions of pro-inflammatory cytokines and maintained the epithelial cell barrier function and cell viability. The silencing of SIRT3 abolished both the anti-inflammatory effect and the retention of cell integrity in BEAS-2B cells. Together these results indicate that treatment with RvD4 can (i) protect against LPS-induced lung injury by inhibiting inflammation, and (ii) maintain epithelial barrier function via a reduction in the downregulation of SIRT3.
Resolvin D4 可减轻脂多糖诱发的小鼠肺损伤。
急性呼吸窘迫综合征(ARDS)是一种涉及严重肺部炎症的危及生命的疾病。ARDS 中出现的过度氧化应激和持续炎症会导致上皮细胞完整性降低,并通过增加血管通透性造成肺水肿而导致低氧血症。Resolvin D4(RvD4)是由欧米茄-3 多不饱和脂肪酸生物合成的脂质介质之一。它在消除炎症、减少氧化应激和细胞死亡方面发挥作用。我们研究了在脂多糖(LPS)诱导的 ARDS 小鼠模型中施用 RvD4 的治疗潜力。在气管内注射 LPS 的同时,每隔 12 小时通过尾静脉给小鼠注射 RvD4 或生理盐水。RvD4治疗缓解了LPS诱导的肺部炎症细胞浸润,抑制了肺血管通透性的增加,降低了支气管肺泡灌洗液(BALF)中IL-1β、IL-6和TNF-α的水平,并抑制了紧密连接蛋白Zonula occludens-1(Zo-1)和NAD+依赖性去乙酰化酶Sirtuin-3(Sirt3)表达水平的降低。体外实验显示,在 LPS 刺激的 BEAS-2B 细胞中,用 RvD4 处理可抑制促炎细胞因子表达的增加,维持上皮细胞屏障功能和细胞活力。沉默 SIRT3 可消除 BEAS-2B 细胞的抗炎作用和细胞完整性的保持。这些结果表明,用 RvD4 治疗可以:(i) 通过抑制炎症防止 LPS 诱导的肺损伤;(ii) 通过减少 SIRT3 的下调维持上皮细胞屏障功能。
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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
自引率
0.00%
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0
审稿时长
64 days
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