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首页> 外文期刊>Inhalation toxicology >Use of indicator cell lines for determining inflammatory gene changes and screening the inflammatory potential of particulate and non-particulate stimuli.
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Use of indicator cell lines for determining inflammatory gene changes and screening the inflammatory potential of particulate and non-particulate stimuli.

机译：指示细胞系用于确定炎性基因变化和筛选微粒和非微粒刺激物的炎性潜力的用途。

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Ultrafine particulate matter, from environmental or industrial exposure, can induce the expression of inflammatory mediators and promote the production of reactive oxygen species (ROS), which can damage the alveolar epithelium of the lung. Previous studies have shown that various cellular stresses can activate signaling pathways that operate through the specific transcription factors (TF), AP-1, and nuclear factor (NF)-? B that are known to regulate inflammatory gene expression. Persistent inflammation can induce a cascade of events that precedes the development of both acute and chronic fibrosis. From a murine Type II epithelial cell line, MLE15, a stable luciferase-transfected line, MLE15Luc2, was created. The luciferase reporter, operating under the guidance of a truncated human interleukin (IL)-8 promoter, contains NF-? B and AP-1 DNA binding sites. MLE15Luc2 cells were exposed to inflammatory or particulate stimuli, of varying size fractions and composition, under standard culture conditions, and inflammatory gene transcription, represented by luciferase enzyme activity, was determined. I? Ba degradation appeared to be incongruent to changes in luciferase activity. The results were compared to those obtained using a stable luciferase-transfected human cell line, A549Luc1. Time-course data demonstrated increased luciferase enzyme activity, peaking by 6 h postexposure, and returning to baseline by 24 h, regardless of stimulus, in the absence of enhanced cytotoxicity. This suggests that key regulatory functions in these transfected cell lines are not clearly understood. These transfected cell lines may be useful for determining the inflammatory potential of various types of particulate and/or nonparticulate stimuli; however, conclusive signaling information cannot be gained from their use alone.
机译：来自环境或工业环境的超细颗粒物可诱导炎症介质的表达并促进活性氧（ROS）的产生，而活性氧可损害肺泡上皮。先前的研究表明，各种细胞应激可以激活通过特定转录因子（TF），AP-1和核因子（NF）-β起作用的信号通路。已知调节炎症基因表达的B。持续性炎症会诱发一系列急性和慢性纤维化之前的事件。从鼠II型上皮细胞系MLE15，创建了稳定的萤光素酶转染的系MLE15Luc2。在截短的人白介素（IL）-8启动子的指导下运行的荧光素酶报道分子含有NF-β。 B和AP-1 DNA结合位点。在标准培养条件下，将MLE15Luc2细胞暴露于大小变化和组成不同的炎症或颗粒刺激物中，并测定以萤光素酶活性为代表的炎症基因转录。一世？ Ba的降解似乎与萤光素酶活性的变化无关。将结果与使用稳定的荧光素酶转染的人类细胞系A549Luc1进行比较。时程数据表明，在没有增强的细胞毒性的情况下，无论刺激如何，荧光素酶活性均增加，在暴露后6 h达到峰值，并在24 h恢复至基线。这表明这些转染细胞系中的关键调控功能尚不清楚。这些转染的细胞系可用于确定各种类型的微粒和/或非微粒刺激物的炎症潜能。但是，不能仅从单独使用中获得结论性信令信息。

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