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首页> 外文期刊>American Journal of Physiology >Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells.
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Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells.

机译：一氧化氮增加了IL-8基因的转录和mRNA的稳定性，从而增强了肺上皮细胞中IL-8基因的表达。

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摘要

Interleukin (IL)-8, a C-X-C chemokine, is a potent chemoattractant and an activator for neutrophils, T cells, and other immune cells. The airway and respiratory epithelia play important roles in the initiation and modulation of inflammatory responses via production of cytokines and surfactant. The association between elevated levels of nitric oxide (NO) and IL-8 in acute lung injury associated with sepsis, acute respiratory distress syndrome, respiratory syncytial virus infection in infants, and other inflammatory diseases suggested that NO may play important roles in the control of IL-8 gene expression in the lung. We investigated the role of NO in the control of IL-8 gene expression in H441 lung epithelial cells. We found that a variety of NO donors significantly induced IL-8 mRNA levels, and the increase in IL-8 mRNA was associated with an increase in IL-8 protein. NO induction of IL-8 mRNA was due to increases in IL-8 gene transcription and mRNA stability. NO induction of IL-8 mRNA levels was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823, inhibitors of soluble guanylate cyclase and protein kinase G, respectively, and 8-bromo-cGMP did not increase IL-8 mRNA levels. This indicated that NO induces IL-8 mRNA levels independently of changes in the intracellular cGMP levels. NO induction of IL-8 mRNA was significantly reduced by inhibitors of extracellular regulated kinase and protein kinase C. IL-8 induction by NO was also reduced by hydroxyl radical scavengers such as dimethyl sulfoxide and dimethylthiourea, indicating the involvement of hydroxyl radicals in the induction process. NO induction of IL-8 gene expression could be a significant contributing factor in the initiation and induction of inflammatory response in the respiratory epithelium.
机译：白介素（IL）-8是一种C-X-C趋化因子，是一种有效的化学引诱剂，是嗜中性粒细胞，T细胞和其他免疫细胞的激活剂。气道和呼吸道上皮在通过细胞因子和表面活性剂的产生引发和调节炎症反应中起重要作用。一氧化氮（NO）和IL-8水平升高与败血症，急性呼吸窘迫综合征，婴儿呼吸道合胞病毒感染以及其他炎性疾病相关的急性肺损伤之间的相关性表明，一氧化氮可能在糖尿病的控制中起重要作用IL-8基因在肺中的表达。我们调查了NO在H441肺上皮细胞中IL-8基因表达的控制中的作用。我们发现，各种NO供体均会显着诱导IL-8 mRNA水平，并且IL-8 mRNA的增加与IL-8蛋白的增加有关。 IL-8 mRNA的NO诱导归因于IL-8基因转录和mRNA稳定性的增加。 1H- [1,2,4]恶二唑[4,3-a]喹喔啉-1-酮和KT-5823（分别是可溶性鸟苷酸环化酶和蛋白激酶G的抑制剂）没有抑制NO诱导IL-8 mRNA的水平。和8-溴-cGMP不会增加IL-8 mRNA水平。这表明NO诱导IL-8 mRNA水平独立于细胞内cGMP水平的变化。 IL-8 mRNA的NO诱导被细胞外调节激酶和蛋白激酶C的抑制剂显着降低。NO诱导的IL-8也被羟自由基清除剂（如二甲基亚砜和二甲基硫脲）降低，表明羟自由基参与诱导处理。 NO诱导IL-8基因表达可能是呼吸上皮炎性反应开始和诱导的重要促成因素。

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