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首页> 外文期刊>International Journal of Environmental Research and Public Health >Diesel Exhaust Particles Induce the Over expression of Tumor Necrosis Factor-α (TNF-α) Gene in Alveolar Macrophages and Failed to Induce Apoptosis through Activation of Nuclear Factor-κB (NF-κB)
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Diesel Exhaust Particles Induce the Over expression of Tumor Necrosis Factor-α (TNF-α) Gene in Alveolar Macrophages and Failed to Induce Apoptosis through Activation of Nuclear Factor-κB (NF-κB)

机译：柴油机排气颗粒诱导肺泡巨噬细胞中的肿瘤坏死因子-α（TNF-α）基因过表达，并且无法通过激活核因子-κB（NF-κB）诱导凋亡。

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Exposure to particulate matter (PM2.5-10), including diesel exhaust particles (DEP) has been reported to induce lung injury and exacerbation of asthma and chronic obstructive pulmonary disease. Alveolar macrophages play a major role in the lung’s response to inhaled particles and therefore, are a primary target for PM2.5-10 effect. The molecular and cellular events underlying DEP-induced toxicity in the lung, however, remain unclear. To determine the effect of DEP on alveolar macrophages, RAW 264.7 cells were grown in RPMI 1640 with supplements until confluency. RAW 264.7 cultures were exposed to Hank’s buffered saline solution (vehicle), vehicle containing an NF-κB inhibitor, BAY11-7082 (25μM with 11/2 hr pre-incubation), or vehicle containing DEP (250μg/ml) in the presence or absence of BAY11-7082 (25μM with 11/2 hr pre-incubation) for 4 hr and TNF-α release was determined by enzyme-linked immunosorbent assay and confirmed by western blots. RAW 264.7 apoptotic response was determined by DNA fragmentation assays. U937 cells treated with campothecin (4 μg/ml x 3 hr), an apoptosis-inducing agent, were used as positive control. We report that exposure to the carbonaceous core of DEP induces significant release of TNF-α in a concentration-dependent fashion (31 ± 4 pg/ml, n = 4, p = 0.08; 162 ± 23 pg/ml, n = 4, p < 0.05; 313 ± 31 pg/ml, n = 4, p < 0.05 at 25, 100, and 250 μg/ml, respectively). DEP exposure, however, failed to induce any apoptotic response in RAW 264.7 cells. Moreover, inhibition of NF-κB binding activity has resulted in DEP-induced apoptotic response in alveolar macrophages, as demonstrated by the NF-κB inhibitor, BAY11-7082 studies. The results of the present study indicate that DEP induce the release of TNF-α in alveolar macrophages, a primary target for inhaled particles effect. DEP-induced TNF-α gene expression is regulated at the transcriptional level by NF-κB. Furthermore, DEP-induced increase in NF-κB-DNA binding activity appears to protect against apoptosis.
机译：据报道，暴露于包括柴油机排气颗粒（DEP）在内的颗粒物（PM2.5-10）会引起肺部损伤，并加剧哮喘和慢性阻塞性肺疾病。肺泡巨噬细胞在肺部对吸入颗粒的反应中起主要作用，因此是PM2.5-10效应的主要靶标。然而，尚不清楚DEP诱导的肺部毒性的分子和细胞事件。为了确定DEP对肺泡巨噬细胞的作用，将RAW 264.7细胞在补充剂的RPMI 1640中生长直至融合。将RAW 264.7培养物暴露于Hank缓冲盐溶液（媒介），含有NF-κB抑制剂的载剂，BAY11-7082（25μM，预孵育11/2小时）或含有DEP（250μg/ ml）的载剂中。 BAY11-7082（25μM，预孵育11/2 hr）不存在4 hr，通过酶联免疫吸附测定确定TNF-α的释放，并通过Western blot确认。通过DNA片段化测定法确定RAW 264.7细胞凋亡反应。用凋亡诱导剂喜树碱（4μg/ ml x 3 hr）处理的U937细胞用作阳性对照。我们报告说，暴露于DEP的碳质核以浓度依赖的方式诱导TNF-α的大量释放（31±4 pg / ml，n = 4，p = 0.08; 162±23 pg / ml，n = 4， p <0.05; 313±31 pg / ml，n = 4，分别在25、100和250μg/ ml时p <0.05）。然而，DEP暴露未能在RAW 264.7细胞中诱导任何凋亡反应。此外，如NF-κB抑制剂BAY11-7082研究所证实的，对NF-κB结合活性的抑制导致DEP诱导的肺泡巨噬细胞凋亡反应。本研究的结果表明，DEP诱导了肺泡巨噬细胞中TNF-α的释放，肺泡巨噬细胞是吸入颗粒效应的主要靶标。 DEP诱导的TNF-α基因表达在转录水平上受NF-κB调控。此外，DEP诱导的NF-κB-DNA结合活性增加似乎可以防止细胞凋亡。

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