Inhibition of gp130 alleviates LPS‑induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathway
Inhibition of gp130 alleviates LPS‑induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathway
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抑制 gp130 通过 JAK1/STAT3 信号通路减轻细胞凋亡和炎症，从而减轻 LPS™ 诱导的肺损伤
DOI：
10.1007/s00011-022-01686-9
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通讯作者：
Lei Zhu
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作者：
Fan Xu;Sijiao Wang;Yali Wang;Lijuan Hu;Lei Zhu
背景与目的急性肺损伤或急性呼吸窘迫综合征(ALI/ARDS)是一种危及生命的呼吸系统疾病。Gp130是一种信号转导受体，参与多种重要的生物学过程。Gp130在ALI/ARDS中的生物学功能尚不清楚。本研究旨在探讨gp130在脂多糖(LPS)致肺损伤中的作用及其可能机制。苏木精-伊红染色和支气管肺泡灌洗液分析评价肺损伤程度。采用TUNEL染色、流式细胞仪和免疫印迹等方法检测细胞凋亡率。用RT-α、免疫印迹和免疫组织化学方法检测Gp130、IL-6、IL-10、肿瘤坏死因子-STAT3和JAK1/STAT3信号通路相关蛋白的表达。抑制gp130可改善内毒素诱导的小鼠肺组织炎症浸润和肺泡塌陷，降低IL-6和肿瘤坏死因子-α水平，升高IL-10水平，减少细胞凋亡。同时，抑制gp130可减少脂多糖诱导的BEAS-2B细胞的炎症反应和细胞凋亡。此外，p-JAK1和p-STAT3的表达在内毒素刺激后升高，抑制gp130后表达降低，提示gp130可能通过调节JAK1/STAT3信号通路调节炎症反应和细胞凋亡，从而减轻内毒素诱导的肺损伤。Gp130可能成为ALI/ARDS的潜在治疗靶点。
Background and objectiveAcute lung injury or acute respiratory distress syndrome (ALI/ARDS) is a life-threatening respiratory disease. Gp130 is a signal transduction receptor that participates in a variety of essential biological processes. The biological function of gp130 in ALI/ARDS is unclear. This study aims to investigate the roles and potential mechanisms of gp130 in lung injury induced by lipopolysaccharide (LPS).MethodsThe ALI/ARDS mouse model was established using intratracheal LPS administration. Hematoxylin and eosin staining and bronchoalveolar lavage fluid analysis were used to evaluate the degree of lung injury. Cell apoptosis was assessed by TUNEL staining, flow cytometry, and western blot. Then the expression of gp130, IL-6, IL-10, TNF-α, and the JAK1/STAT3 signaling pathway-related proteins was assessed by RT-PCR, western blot, and immunohistochemistry.ResultsThe expression of gp130 increased after 24 h of LPS treatment. Inhibiting gp130 improved inflammatory infiltration and alveolar collapsed, decreased IL-6 and TNF-α levels, raised IL-10 levels, and decreased cell apoptosis in LPS-induced mice. Meanwhile, suppressing gp130 reduced the inflammatory response and cell apoptosis in LPS-induced Beas-2B cells. Furthermore, p-JAK1 and p-STAT3 expressions were elevated after LPS stimulation and decreased following gp130 inhibition, suggesting that gp130 may regulate the JAK1/STAT3 signaling pathway in LPS-induced mice and Beas-2B cells.ConclusionThe findings suggest that gp130 regulates the inflammatory response and cell apoptosis through the JAK1/STAT3 signaling pathway, thereby mitigating LPS-induced lung injury. Gp130 may be a potential therapeutic target for ALI/ARDS.