Alpha particles induce the production of interleukin-8 by human cells
Alpha particles induce the production of interleukin-8 by human cells
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DOI：
10.2307/3580049
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发表时间：
1999-07-01
影响因子：
3.4
通讯作者：
Lehnert, BE
中科院分区：
文献类型：
--
作者：
Narayanan, PK;LaRue, KEA;Lehnert, BE
肺微环境是吸入氡及其子体所释放的阿尔法粒子的主要靶点，虽然最近阿尔法粒子暴露与细胞外和细胞内活性氧物种的产生有关(ROS；癌症研究57,3963-3971,1997)，但对阿尔法粒子暴露如何影响呼吸道中氧化应激相关介质的产生知之甚少。白细胞介素8(IL8)是一种公认的细胞因子，它是一种强有力的趋化因子和多形核白细胞的激活剂，氧化应激可上调编码IL8的基因在多种细胞类型中的表达。在本研究中，我们开始研究在α粒子照射的正常人肺成纤维细胞中ROS的产生和IL8的产生之间的潜在联系，ELISA法发现，低剂量的α粒子(3.6-19cGy)照射后30分钟，成纤维细胞的IL8蛋白的产生就显著增加。Northern印迹分析表明，这种增加与IL8 mRNA水平的增加有关，细胞暴露在超氧化物歧化酶和二甲基亚砜等抗氧化剂存在的阿尔法粒子中，导致细胞外IL8蛋白水平显著降低。在用转录抑制剂地塞米松处理的细胞中也得到了类似的结果，我们的结果表明，α粒子诱导的ns产生的增加与ROS产生的增加在时间上是平行的，可以想见，这种由a粒子诱导的ILS的产生可能有助于下呼吸道的炎症反应。此外，IL8的促有丝分裂作用可能是呼吸道上皮细胞对吸入氡和氡子体以及可能与ROS相关的其他应激反应的增殖反应的一个因素，(C)1999 br辐射研究学会。
The pulmonary microenvironment is a primary target for alpha particles like those emitted by inhaled radon and its progeny, While exposure to alpha particles has recently been associated with the generation of extracellular and intracellular reactive oxygen species (ROS; Cancer Res. 57, 3963-3971, 1997), little is known about how exposure to alpha particles mag affect the generation of oxidative stress-related mediators in the respiratory tract. Interleukin-8 (IL8) is a cytokine recognized for its potent role as a chemoattractant and activator of polymorphonuclear leukocytes, Oxidative stress can up-regulate expression of the gene that encodes IL8 (IL8) in a variety of cell types, In this study, we set out to investigate a potential linkage between the generation of ROS and production of ILS in alpha-particle-irradiated normal human lung fibroblasts, ELISA revealed that exposure of the fibroblasts to low doses of alpha particles (3.6-19 cGy) caused significant increases in generation of the IL8 protein as early as 30 min after irradiation. Northern blot analyses revealed that such increases were associated with increased IL8 mRNA levels, Cells exposed to alpha particles in the presence of antioxidants, i.e. superoxide dismutase and dimethyl sulfoxide, resulted in significant decreases in extracellular IL8 protein levels. Similar results were obtained with cells treated with dexamethasone, an inhibitor of transcription, Our results indicate that alpha-particle-induced increases in production of ns occur temporally in parallel with elevated production of ROS, Conceivably, such production of ILS induced by a particles may contribute to an inflammatory response in the lower respiratory tract. Additionally, the promitogenic effects of IL8 may be a factor in hyperplastic responses in the airway epithelial cells to inhaled radon and radon progeny and perhaps other stresses associated with ROS, (C) 1999 br Radiation Research Society.