Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors.
Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors.
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DOI：
10.1371/journal.pone.0120510
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Davies DE
中科院分区：
文献类型：
--
作者：
Bucchieri F;Marino Gammazza A;Pitruzzella A;Fucarino A;Farina F;Howarth P;Holgate ST;Zummo G;Davies DE
流行病学研究已经证明了空气污染和哮喘之间的重要联系。在这些污染物中，环境香烟烟雾是哮喘发病和加重的危险因素。作为吸入环境的屏障，支气管上皮是暴露于香烟烟雾的关键结构。由于哮喘供体的原代支气管上皮细胞（PBEC）对氧化剂诱导的细胞凋亡更敏感，我们假设它们对香烟烟雾诱导的细胞死亡也敏感。将正常和哮喘供体的PBEC暴露于香烟烟雾提取物（CSE）;通过荧光激活细胞分选评估细胞存活和凋亡，并评估抗氧化剂的保护作用。采用半胱天冬酶抑制剂和凋亡诱导因子（AIF）免疫荧光染色法评价细胞死亡机制。PBEC培养物暴露于CSE导致细胞死亡的剂量依赖性增加。在20%CSE下，来自哮喘供体的PBEC比来自非哮喘对照的细胞表现出显著更多的凋亡。还原型谷胱甘肽（GSH），而不是抗坏血酸（AA），对CSE诱导的细胞凋亡的保护。为了研究CSE诱导的细胞凋亡的机制，测试了半胱天冬酶-3或-9抑制剂，但这些抑制剂未能阻止细胞凋亡;相反，CSE促进AIF从线粒体的核转位。GSH减少核AIF阳性细胞的数量，而AA无效。我们的研究结果表明，哮喘供体的PBEC更容易受到CSE诱导的凋亡。这种反应涉及AIF，它与DNA损伤和ROS介导的细胞死亡有关。上皮细胞对CSE的易感性可能有助于环境烟草烟雾对哮喘的影响。
Epidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke. Since primary bronchial epithelial cells (PBECs) from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death. PBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE); cell survival and apoptosis were assessed by fluorescence-activated cell sorting, and protective effects of antioxidants evaluated. The mechanism of cell death was evaluated using caspase inhibitors and immunofluorescent staining for apoptosis-inducing factor (AIF). Exposure of PBEC cultures to CSE resulted in a dose-dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibited significantly more apoptosis than cells from non-asthmatic controls. Reduced glutathione (GSH), but not ascorbic acid (AA), protected against CSE-induced apoptosis. To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear translocation of AIF from the mitochondria. GSH reduced the number of nuclear-AIF positive cells whereas AA was ineffective. Our results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthma.
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影响因子：
6.1
作者：
CURVALL, M;ENZELL, CR;PETTERSSON, B
通讯作者：
PETTERSSON, B
影响因子：
--
作者：
Bazzini, Claudia;Rossetti, Valeria;Garavaglia, Maria Lisa
通讯作者：
Garavaglia, Maria Lisa
DOI：
10.1164/ajrccm/137.1.57
发表时间：
1988-01-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
POSTMA, DS;RENKEMA, TEJ;KAUFFMAN, H
通讯作者：
KAUFFMAN, H
DOI：
10.1165/rcmb.2005-0433oc
发表时间：
2006-08-01
影响因子：
6.4
作者：
Merendino, Anna M.;Bucchieri, Fabio;Vignola, Antonio M.
通讯作者：
Vignola, Antonio M.
DOI：
10.1165/rcmb.2010-0029oc
发表时间：
2011-06-01
影响因子：
6.4
作者：
Freishtat, Robert J.;Watson, Alan M.;Hoffman, Eric P.
通讯作者：
Hoffman, Eric P.