Neutrophil-Derived IL-17 Promotes Ventilator-Induced Lung Injury via p38 MAPK/MCP-1 Pathway Activation.
Neutrophil-Derived IL-17 Promotes Ventilator-Induced Lung Injury via p38 MAPK/MCP-1 Pathway Activation.
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DOI：
10.3389/fimmu.2021.768813
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发表时间：
2021
影响因子：
7.3
通讯作者：
Pan L
中科院分区：
文献类型：
--
作者：
Liao X;Zhang W;Dai H;Jing R;Ye M;Ge W;Pei S;Pan L
呼吸机引起的肺损伤（VILI）是机械通气最常见的并发症之一，可严重影响健康。 VILI似乎涉及过度的炎症反应，但其发病机制尚未阐明。由于白细胞介素 17 (IL-17) 在免疫系统以及感染性和炎症性疾病的发展中发挥着关键作用，因此我们在此研究了它是否在 VILI 中发挥作用。在 VILI 小鼠模型中，高潮气量机械通气促进肺中性粒细胞的积累，导致肺中 IL-17 水平增加，进而通过 p38 丝裂原激活蛋白激酶上调巨噬细胞趋化蛋白-1。中性粒细胞的消耗会降低小鼠中 IL-17 的产生，而抑制 IL-17 会显着减少 HTV 诱导的肺损伤和炎症反应。这些结果在体外使用 RAW264.7 巨噬细胞培养物得到证实。我们的结果表明，IL-17 在 VILI 中发挥促炎作用，可以作为其治疗的新靶点。
Ventilator-induced lung injury (VILI) is one of the most common complications of mechanical ventilation and can severely affect health. VILI appears to involve excessive inflammatory responses, but its pathogenesis has not yet been clarified. Since interleukin-17 (IL-17) plays a critical role in the immune system and the development of infectious and inflammatory diseases, we investigated here whether it plays a role in VILI. In a mouse model of VILI, mechanical ventilation with high tidal volume promoted the accumulation of lung neutrophils, leading to increased IL-17 levels in the lung, which in turn upregulated macrophage chemoattractant protein-1 via p38 mitogen-activated protein kinase. Depletion of neutrophils decreases the production IL-17 in mice and inhibition of IL-17 significantly reduced HTV-induced lung injury and inflammatory response. These results were confirmed in vitro using RAW264.7 macrophage cultures. Our results suggest that IL-17 plays a pro-inflammatory role in VILI and could serve as a new target for its treatment.