Intracellular glutathione in stretch-induced cytokine release from alveolar type-2 like cells
Intracellular glutathione in stretch-induced cytokine release from alveolar type-2 like cells
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DOI：
10.1111/j.1440-1843.2003.00527.x
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发表时间：
2004-03-01
期刊：
影响因子：
6.9
通讯作者：
Quinn, DA
中科院分区：
文献类型：
--
作者：
Jafari, B;Ouyang, B;Quinn, DA
目的：呼吸机诱导的肺损伤（VILI）以炎性细胞因子的释放为特征，但其机制尚不清楚。我们假设牵张诱导的细胞因子的产生依赖于氧化剂的释放，并受细胞内谷胱甘肽（GSH）抑制核因子κ B的调节。（NF-κ B）和激活蛋白-1（AP-1）结合。将2型样肺泡上皮细胞（A549）以15%应变以20个周期/min暴露于有或无N-乙酰半胱氨酸（NAC）的周期性拉伸4 h。或谷胱甘肽单乙酯（GSH-e），以增加细胞内的GSH，或丁硫基亚砜（BSO），以耗尽细胞内GSH.Results：循环拉伸最初引起细胞内GSH的下降和异前列腺素，氧化损伤的标志物的水平上升。随后是细胞内GSH的显著增加和异前列烷的减少。当细胞内GSH进一步被NAC或GSH-e增加时，牵张诱导的IL-8和IL-6的产生被显著抑制（P < 0.0001）。当BSO耗竭细胞内GSH时，牵张诱导的IL-8和IL-6产生增加（P < 0.0001）。NAC阻断牵张诱导的NF-κ B和AP-1结合，抑制IL-8 mRNA的表达。结论：我们得出结论，氧化剂释放可能在肺细胞牵张诱导的细胞因子释放中发挥作用，抗氧化剂，增加细胞内GSH，可能保护肺细胞免受牵张诱导的损伤。
Objective: Ventilator-induced lung injury (VILI) is characterized by release of inflammatory cytokines, but the mechanisms are not well understood. We hypothesized that stretch-induced cytokine production is dependent on oxidant release and is regulated by intracellular glutathione (GSH) inhibition of nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1) binding.Methodology: Type 2-like alveolar epithelial cells (A549) were exposed to cyclic stretch at 15% strain for 4 h at 20 cycles/min with or without N-acetylcysteine (NAC) or glutathione monoethylester (GSH-e) to increase intracellular GSH, or buthionine sulfoximine (BSO), to deplete intracellular GSH.Results: Cyclic stretch initially caused a decline in intracellular GSH and a rise in the levels of isoprostane, a marker of oxidant injury. This was followed by a significant increase in intracellular GSH and a decrease in isoprostane. Stretch-induced IL-8 and IL-6 production were significantly inhibited when intracellular GSH was further increased by NAC or GSH-e (P < 0.0001). Stretch-induced IL-8 and IL-6 production were augmented when intracellular GSH was depleted by BSO (P < 0.0001). NAC blocked stretch-induced NF-kappaB and AP-1 binding and inhibited IL-8 mRNA expression.Conclusions: We conclude that oxidant release may play a role in lung cell stretch-induced cytokine release, and antioxidants, which increase intracellular GSH, may protect lung cells against stretch-induced injury.