Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Int Immunopharmacol. 2024 Nov 15;141:112805. doi: 10.1016/j.intimp.2024.112805. Epub 2024 Aug 14.
During the inflammatory storm of sepsis, a significant quantity of neutrophil extracellular traps (NETs) are generated, which act as a double-edged sword and not only impede the invasion of foreign microorganisms but also exacerbate organ damage. This study provides evidence that NETs can cause damage to alveolar epithelial cells in vitro. The sepsis model developed in this study showed a significant increase in NETs in the bronchoalveolar lavage fluid (BALF). The development of NETs has been shown to increase the lung inflammatory response and aggravate injury to alveolar epithelial cells. Bay-117082, a well-known NF-κB suppressor, is used to modulate inflammation. This analysis revealed that Bay-117082 efficiently reduced total protein concentration, myeloperoxidase activity, and inflammatory cytokines in BALF. Moreover, Bay-117082 inhibited the formation of NETs, which in turn prevented the activation of the pore-forming protein gasdermin D (GSDMD). In summary, these results indicated that excessive NET production during sepsis exacerbated the onset and progression of acute lung injury (ALI). Therefore, Bay-117082 could serve as a novel therapeutic approach for ameliorating sepsis-associated ALI.
在脓毒症的炎症风暴中，会产生大量的中性粒细胞胞外诱捕网（NETs），它们犹如一把双刃剑，不仅阻碍了外来微生物的入侵，还加重了器官损伤。本研究提供了证据表明 NETs 可导致体外肺泡上皮细胞损伤。本研究中建立的脓毒症模型显示，支气管肺泡灌洗液（BALF）中的 NETs 显著增加。研究表明，NETs 的发展会增加肺部炎症反应，并加重对肺泡上皮细胞的损伤。Bay-117082 是一种著名的 NF-κB 抑制剂，用于调节炎症。该分析表明，Bay-117082 可有效降低 BALF 中的总蛋白浓度、髓过氧化物酶活性和炎症细胞因子。此外，Bay-117082 抑制了 NETs 的形成，进而阻止了孔形成蛋白 gasdermin D（GSDMD）的激活。综上所述，这些结果表明脓毒症期间过度的 NET 产生加重了急性肺损伤（ALI）的发生和进展。因此，Bay-117082 可能成为改善脓毒症相关 ALI 的一种新的治疗方法。
