Diesel exhaust particles upregulate eotaxin gene expression in human bronchial epithelial cells via nuclear factor-κB-dependent pathway
Diesel exhaust particles upregulate eotaxin gene expression in human bronchial epithelial cells via nuclear factor-κB-dependent pathway
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DOI：
10.1152/ajplung.00358.2002
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发表时间：
2003-06-01
影响因子：
4.9
通讯作者：
Kudoh, S
中科院分区：
文献类型：
--
作者：
Takizawa, H;Abe, S;Kudoh, S
源自柴油发动机的细颗粒——柴油机尾气颗粒（DEP）已被证明可以在体外增强人气道上皮细胞中几种炎症细胞因子的基因表达。然而，目前尚不清楚 DEP 是否对嗜酸性粒细胞趋化因子的表达和产生有任何影响，嗜酸性粒细胞趋化因子是一种重要的趋化因子，参与嗜酸性粒细胞募集到气道中。我们通过使用传统的悬浮 DEP 和最近建立的柴油废气体外细胞暴露系统研究了 DEP 的影响（Abe S、Takizawa H、Sugarara I 和 Kudoh S、Am J Respir Cell Mol Biol 22：296 - 303，2000）。通过特异性 ELISA 评估，DEP 对正常人外周气道上皮细胞以及支气管上皮细胞系 BET-1A 的嗜酸细胞趋化因子产生具有剂量依赖性刺激作用。 RT-PCR 显示 DEP 增加了 mRNA 水平。 DEP 对 IL-13 刺激的嗜酸细胞趋化因子表达具有累加效应。如之前报道的，DEP 通过 EMSA 诱导 NF-kappaB 激活，但根据蛋白质印迹分析，不诱导信号转导子和转录激活子 (STAT) 6 激活。最后，抗氧化剂（N-乙酰半胱氨酸和吡咯烷二硫代氨基甲酸酯）抑制 NF-kappaB 激活但不影响 STAT6 激活，几乎完全减弱 DEP 诱导的嗜酸细胞趋化因子的产生，而这些药物未能减弱 IL-13 诱导的嗜酸细胞趋化因子的产生。这些发现表明，DEP 通过 NF-kappaB 依赖但不依赖 STAT6 的途径刺激嗜酸细胞趋化因子基因表达。
Fine particles derived from diesel engines, diesel exhaust particles (DEP), have been shown to augment gene expression of several inflammatory cytokines in human airway epithelial cells in vitro. However, it remains unclear whether or not DEP have any effect on the expression and production of eotaxin, an important chemokine involved in eosinophil recruitment into the airways. We studied the effects of DEP by using a conventional suspended DEP and by a recently established in vitro cell exposure system to diesel exhaust (Abe S, Takizawa H, Sugawara I, and Kudoh S, Am J Respir Cell Mol Biol 22: 296 - 303, 2000). DEP showed a dose-dependent stimulatory effect on eotaxin production by normal human peripheral airway epithelial cells as well as by bronchial epithelial cell line BET-1A as assessed by specific ELISA. mRNA levels increased by DEP were shown by RT-PCR. DEP showed an additive effect on IL-13-stimulated eotaxin expression. DEP induced NF-kappaB activation by EMSA as previously reported but did not induce signal transducer and activator of transcription ( STAT) 6 activation according to Western blot analysis. Finally, antioxidant agents (N-acetyl cysteine and pyrrolidine dithiocarbamate), which inhibited NF-kappaB activation but failed to affect STAT6 activation, almost completely attenuated DEP-induced eotaxin production, whereas these agents failed to attenuate IL-13-induced eotaxin production. These findings suggested that DEP stimulated eotaxin gene expression via NF-kappaB-dependent, but STAT6-independent, pathways.