暴露于乙醇的肺纤维细胞会导致气道上皮质屏障功能障碍
Viranuj Sueblinvong1, Xian Fan1, Craishun Hart1
1Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Alcohol, clinical & experimental research
|October 21, 2023
概括
长期使用酒精会损害肺纤维细胞,损害呼吸道上皮质屏障功能. 这通过增加转化生长因子-β1 (TGFβ1) 和降低颗粒细胞-巨细胞殖民地刺激因子 (GM-CSF) 来发生,从而增加肺损伤的易感性.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 慢性酒精摄入与肺损伤和败血症期间损伤的修复有关.
- 酒精通过改变转化生长因子-β1 (TGFβ1) 和颗粒细胞-巨细胞殖民地刺激因子 (GM-CSF) 的表达和信号来破坏表皮屏障稳定.
- 暴露于乙醇的肺纤维细胞 (LF) 可能导致呼吸道上皮质屏障功能发生变化.
研究的目的:
- 调查暴露于乙醇的肺纤维细胞 (LF) 是否调节TGFβ1和GM-CSF,影响呼吸道上皮质屏障功能.
- 阐明TGFβ1信号在酒精诱导的肺损伤中的作用.
主要方法:
- 人类或老鼠的LF与乙醇或不含乙醇培养,并与空气道上皮细胞 (AEC) 在Transwell支上共同培养.
- 测量了体电阻 (TER),并分析了AEC的紧结蛋白 (ZO-1) 和介质细胞蛋白表达.
- 条件介质中的TGFβ1和GM-CSF水平通过ELISA量化;使用抑制剂或中和抗体阻止TGFβ1活性.
主要成果:
- 与暴露于乙醇的LF (ELF) 共同培养的AEC表现出TER和ZO-1表达的减少,原1A1型和α-平滑肌肉活性增加.
- 在条件介质中,ELF共同培养显示了活性TGFβ1的增加和GM-CSF水平的降低.
- 阻止TGFβ1活动完全阻止了ELF对AEC的有害影响.
结论:
- 暴露于乙醇的肺炎会通过近信号传递诱导空气道上皮质屏障功能障碍,通过天真的AEC.
- 这种功能障碍是由TGFβ1激活和GM-CSF抑制介导的.
- 这些发现表明,酒精诱导的呼吸道上皮质完整性受损的机制,增加肺损伤的易感性.
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