Reversal of cigarette smoke extract-induced sinonasal epithelial cell barrier dysfunction through Nrf2 Activation.
Reversal of cigarette smoke extract-induced sinonasal epithelial cell barrier dysfunction through Nrf2 Activation.
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DOI：
10.1002/alr.21827
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发表时间：
2016-11
影响因子：
6.4
通讯作者：
Ramanathan, Murugappan, Jr.
中科院分区：
文献类型：
--
作者：
Tharakan, Anuj;Halderman, Ashleigh A.;Lane, Andrew P.;Biswal, Shyam;Ramanathan, Murugappan, Jr.
环境因素，如吸入污染物，如香烟烟雾，可能在上呼吸道疾病，包括慢性鼻窦炎（CRS）中发挥重要作用。最近的研究表明，吸烟可能通过环境氧化应激相关途径导致气道上皮细胞屏障功能受损。本研究的目的是探讨增强人体主要抗氧化系统Nrf2是否可以改善香烟烟雾引起的鼻窦上皮细胞屏障功能障碍。人鼻窦上皮细胞（HSNECs）从对照患者在气液界面培养。用香烟烟雾提取物（CSE）刺激hsnec，有或没有Nrf2的药理激活。然后用共聚焦显微镜对HSNECs进行上皮细胞连接蛋白ZO-1和JAM-A的染色。此外，在CSE刺激前后的培养中测量了跨上皮电阻（TER）。CSE刺激引起上皮连接蛋白ZO-1和JAM-A的整体破坏，并伴有TER水平的降低。在CSE刺激前Nrf2水平的增强与细胞表面ZO-1和JAM-A水平的定位增加以及TER水平的统计学显著增加有关。这是第一个证明香烟引起的鼻窦上皮细胞屏障功能障碍可通过Nrf2激活逆转的研究。Nrf2抗氧化途径可能是香烟相关鼻窦炎症的潜在治疗靶点。
Environmental factors such as inhaled pollutants like cigarette smoke may play a significant role in diseases of the upper airway including chronic rhinosinusitis (CRS). Recent studies have shown that cigarette smoke causes impaired airway epithelial cell barrier function likely through environmental oxidative stress related pathways. The purpose of this study is to explore whether enhancing Nrf2, the body’s master antioxidant system, can ameliorate cigarette smoke induced sinonasal epithelial cell barrier dysfunction. Human Sinonasal epithelial cells (HSNECs) were grown from control patients at the air-liquid interface. HSNECs were stimulated with cigarette smoke extract (CSE) with and without pharmacologic activation of Nrf2. HSNECs were then stained for the epithelial cell junctional proteins ZO-1 and JAM-A using confocal microscopy. In addition trans-epithelial electrical resistance (TER) was measured in cultures before and after stimulation with CSE CSE stimulation caused a global disruption of the epithelial junctional proteins ZO-1 and JAM-A along with an associated decrease in TER levels. Enhancing Nrf2 levels prior to stimulation with CSE was associated with increased localization of ZO-1 and JAM-A levels at the cell surface and statistically significant increases in TER levels. This is the first study to demonstrate that cigarette smoke induced sinonasal epithelial cell barrier dysfunction is reversible by Nrf2 activation. The Nrf2 antioxidant pathway may represent a potential therapeutic target for cigarette smoke associated sinonasal inflammation.
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影响因子：
6.4
作者：
Kohanski MA;Tharakan A;Lane AP;Ramanathan M Jr
通讯作者：
Ramanathan M Jr
影响因子：
6.4
作者：
Paris, Gina;Pozharskaya, Tatyana;Asempa, Tomefa;Lane, Andrew P.
通讯作者：
Lane, Andrew P.
DOI：
10.1165/ajrcmb.23.4.3959
发表时间：
2000-10-01
影响因子：
6.4
作者：
Rusznak, C;Mills, PR;Lozewicz, S
通讯作者：
Lozewicz, S
影响因子：
6.4
作者：
Lee, Woo Hyun;Hong, Seung-No;Kim, Jeong-Whun
通讯作者：
Kim, Jeong-Whun
影响因子：
6.4
作者：
Reh, Douglas D.;Higgins, Thomas S.;Smith, Timothy L.
通讯作者：
Smith, Timothy L.