Pulmonary instillation of MWCNT increases lung permeability, decreases gp130 expression in the lungs, and initiates cardiovascular IL-6 transsignaling.
Pulmonary instillation of MWCNT increases lung permeability, decreases gp130 expression in the lungs, and initiates cardiovascular IL-6 transsignaling.
复制标题
肺部灌注 MWCNT 会增加肺通透性，降低肺部 gp130 表达，并启动心血管 IL-6 转信号。
DOI：
10.1152/ajplung.00384.2014
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Wingard,ChristopherJ
中科院分区：
文献类型：
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作者：
Thompson,LeslieC;Holland,NathanA;Snyder,RyanJ;Luo,Bin;Becak,DanielP;Odom,JillianT;Harrison,BenjaminS;Brown,JaredM;Gowdy,KymberlyM;Wingard,ChristopherJ
多壁碳纳米管（MWCNT）的肺灌注有可能促进心血管紊乱，但目前尚不清楚负责的机制。我们假设，暴露于多壁碳纳米管将导致增加上皮屏障通透性24小时后，extraperitoneal，并启动一个信号传导过程，涉及IL-6/gp 130 transsignaling在外周血管组织。为了验证这一假设，我们使用正常人支气管上皮原代细胞评估了1和10 μg/cm 2 MWCNT对跨上皮电阻（TEER）和屏障蛋白表达以及体外细胞活化的影响。使用100 μg MWCNT滴注的雄性Sprague-Dawley大鼠进行的平行研究测量了支气管肺泡灌洗（BAL）分类细胞计数、BAL液总蛋白和肺水/组织重量比，并定量了IL-6、可溶性IL-6 r和可溶性gp 130的血清浓度。主动脉切片进行化学染色检测gp 130表达，并在大鼠肺、心脏和主动脉组织匀浆中评价gp 130 mRNA/蛋白表达。我们的体外研究结果表明，10 μg/cm 2 MWCNT相对于载体降低了TEER和闭合小带-1表达的发展。在大鼠中，多壁碳纳米管滴注增加了BAL蛋白、肺水和诱导的肺嗜酸性粒细胞增多。多壁碳纳米管暴露组血清可溶性gp 130浓度降低，主动脉内皮gp 130表达增加，肺gp 130表达下调。我们认为，肺暴露于多壁碳纳米管可以表现为减少上皮屏障和激活血管gp 130相关的信号转导，可能会促进心血管紊乱的易感性。
Pulmonary instillation of multiwalled carbon nanotubes (MWCNT) has the potential to promote cardiovascular derangements, but the mechanisms responsible are currently unclear. We hypothesized that exposure to MWCNT would result in increased epithelial barrier permeability by 24 h postexposure and initiate a signaling process involving IL-6/gp130 transsignaling in peripheral vascular tissue. To test this hypothesis we assessed the impact of 1 and 10 μg/cm2MWCNT on transepithelial electrical resistance (TEER) and expression of barrier proteins and cell activation in vitro using normal human bronchial epithelial primary cells. Parallel studies using male Sprague-Dawley rats instilled with 100 μg MWCNT measured bronchoalveolar lavage (BAL) differential cell counts, BAL fluid total protein, and lung water-to-tissue weight ratios 24 h postexposure and quantified serum concentrations of IL-6, soluble IL-6r, and soluble gp130. Aortic sections were examined immunohistochemically for gp130 expression, and gp130 mRNA/protein expression was evaluated in rat lung, heart, and aortic tissue homogenates. Our in vitro findings indicate that 10 μg/cm2MWCNT decreased the development of TEER and zonula occludens-1 expression relative to the vehicle. In rats MWCNT instillation increased BAL protein, lung water, and induced pulmonary eosinophilia. Serum concentrations of soluble gp130 decreased, aortic endothelial expression of gp130 increased, and expression of gp130 in the lung was downregulated in the MWCNT-exposed group. We propose that pulmonary exposure to MWCNT can manifest as a reduced epithelial barrier and activator of vascular gp130-associated transsignaling that may promote susceptibility to cardiovascular derangements.