Zhao Yan, Cheng Li, Song Zhi-Xin, Deng Xin-Yu, He Jing, Deng Wang, Wang Dao-Xin
Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2016 Apr 20;37(4):494-498. doi: 10.3969/j.issn.1673-4254.2017.04.12.
To investigate the role of interleukin-17 (IL-17) in alveolar fluid clearance in mice with acute lung injury (ALI) and explore the possible mechanism.
Sixteen IL-17-knockout mice and 16 wild-type mice were both randomized for intratracheal instillation of PBS (control) on lipopolysaccharide (LPS) to induce ALI. Forty-eight hours after the treatments, the wet-dry ratio (W/D) of the lungs, IL-8 in the bronchoalveolar lavage fluid (BALF) and histopathological changes of the lung tissues were examined. The expressions of epithelial sodium channel α subunit (α-ENaC) was detected with Western blotting and liver kinase B1 (LKB1) was detected with immunohistochemistry.
Compared with wild-type mice treated with LPS, IL-17 knockout mice showed significantly decreased W/D of the lungs (9.739∓3.3 vs 5.351∓0.56) and IL-8 level in the BALF (67.50∓7.33 vs 41.00∓3.16 pg/mL) following LPS challenge. Pathological examination revealed reduced alveolar edema fluid aggregations and lower lung injury score in IL-17 knockout mice with also higher expression levels of ENaC and LKB1 compared with the wild-type mice.
Knocking out IL-17 in mice not only alleviates inflammation of the lung tissue following ALI but also reduces the loss of ENaC protein and promotes alveolar fluid clearance, mechanism of which is probably associated with LKB1.
探讨白细胞介素-17(IL-17)在急性肺损伤(ALI)小鼠肺泡液体清除中的作用,并探索其可能机制。
将16只IL-17基因敲除小鼠和16只野生型小鼠随机分为两组,通过气管内滴注脂多糖(LPS)联合磷酸盐缓冲液(PBS)(对照组)诱导ALI。处理48小时后,检测肺组织湿干比(W/D)、支气管肺泡灌洗液(BALF)中IL-8水平及肺组织病理变化。采用蛋白质印迹法检测上皮钠通道α亚基(α-ENaC)的表达,免疫组织化学法检测肝激酶B1(LKB1)的表达。
与LPS处理的野生型小鼠相比,LPS攻击后,IL-17基因敲除小鼠肺组织W/D显著降低(9.739±3.3比5.351±0.56),BALF中IL-8水平显著降低(67.50±7.33比41.00±3.16 pg/mL)。病理检查显示,IL-17基因敲除小鼠肺泡水肿液聚集减少,肺损伤评分降低,且ENaC和LKB1表达水平高于野生型小鼠。
敲除小鼠体内的IL-17不仅可减轻ALI后肺组织炎症,还可减少ENaC蛋白丢失,促进肺泡液体清除,其机制可能与LKB1有关。