Inhibition of gp130 alleviates LPS-induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathway,Inflammation Research

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Inhibition of gp130 alleviates LPS-induced lung injury by attenuating apoptosis and inflammation through JAK1/STAT3 signaling pathway
Inflammation Research ( IF 4.8 ) Pub Date : 2023-01-08 , DOI: 10.1007/s00011-022-01686-9
Fan Xu ₁ , Sijiao Wang ₁ , Yali Wang ₁ , Lijuan Hu ₁ , Lei Zhu _{1,

2}

Affiliation

Background and objective

Acute 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).

Methods

The 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.

Results

The 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.

Conclusion

The 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.

中文翻译：

抑制 gp130 通过 JAK1/STAT3 信号通路减弱细胞凋亡和炎症来减轻 LPS 诱导的肺损伤

背景和目标

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) 诱导的肺损伤中的作用和潜在机制。

方法

使用气管内 LPS 给药建立 ALI/ARDS 小鼠模型。苏木精和伊红染色和支气管肺泡灌洗液分析用于评估肺损伤程度。通过 TUNEL 染色、流式细胞术和蛋白质印迹评估细胞凋亡。然后通过 RT-PCR、蛋白质印迹和免疫组织化学评估 gp130、IL-6、IL-10、TNF-α 和 JAK1/STAT3 信号通路相关蛋白的表达。

结果

LPS 处理 24 小时后 gp130 的表达增加。抑制 gp130 可改善炎症浸润和肺泡塌陷，降低 IL-6 和 TNF-α 水平，升高 IL-10 水平，并减少 LPS 诱导小鼠的细胞凋亡。同时，抑制 gp130 可降低 LPS 诱导的 Beas-2B 细胞的炎症反应和细胞凋亡。此外，p-JAK1 和 p-STAT3 表达在 LPS 刺激后升高，在 gp130 抑制后降低，表明 gp130 可能调节 LPS 诱导的小鼠和 Beas-2B 细胞中的 JAK1/STAT3 信号通路。