NF-kappaB mediates the survival of human bronchial epithelial cells exposed to cigarette smoke extract.
NF-kappaB mediates the survival of human bronchial epithelial cells exposed to cigarette smoke extract.
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NF-kappaB 介导暴露于香烟烟雾提取物的人支气管上皮细胞的存活。
DOI：
10.1186/1465-9921-9-66
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发表时间：
2008-09-23
影响因子：
5.8
通讯作者：
Rennard S
中科院分区：
文献类型：
--
作者：
Liu X;Togo S;Al-Mugotir M;Kim H;Fang Q;Kobayashi T;Wang X;Mao L;Bitterman P;Rennard S
我们以前曾报道，低浓度的香烟烟雾提取物可诱导人支气管上皮细胞DNA损伤，但不会导致细胞凋亡或坏死，IL-6/STAT3信号通路参与了细胞的存活。由于核因子-κB还参与调节细胞的凋亡和存活，本研究旨在探讨核因子-κB在介导细胞对香烟烟雾暴露的细胞存活中的作用。应用核因子-κB的药物抑制剂姜黄素和靶向p65的RNAi阻断核因子-κB信号转导通路。采用彗星试验、活/死细胞毒/活实验和集落形成实验等方法检测细胞凋亡率和细胞存活率。TUNEL法、彗星试验和DNA含量测定表明，香烟烟雾提取物可引起细胞DNA损伤，并使细胞周期停滞于S期，但不能诱导细胞发生凋亡。CSE刺激HBECs的核因子-BclDNA结合活性，上调κ-xl蛋白表达。用药物抑制剂姜黄素(20κM)抑制NF-μB或用小干扰RNA抑制p65可显著增加香烟烟雾暴露所致的细胞死亡。此外，当缺乏p65的细胞暴露在CSE中时，它们不能形成细胞克隆，而它们在常规培养基中表现正常。目前的研究表明，CSE通过激活NF-κB激活HBECs中的NF-kB，上调BclxL，并诱导缺乏p65的细胞死亡。这些结果表明，在香烟烟雾损伤人支气管上皮细胞后，NF-κB的激活调节了细胞的存活。
We have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial cells (HBECs), and that IL-6/STAT3 signaling contributes to the cell survival. Since NF-κB is also involved in regulating apoptosis and cell survival, the current study was designed to investigate the role of NF-κB in mediating cell survival in response to cigarette smoke exposure in HBECs. Both the pharmacologic inhibitor of NF-κB, curcumin, and RNA interference targeting p65 were used to block NF-κB signaling in HBECs. Apoptosis and cell survival were then assessed by various methods including COMET assay, LIVE/DEAD Cytotoxicity/Viability assay and colony formation assay. Cigarette smoke extract (CSE) caused DNA damage and cell cycle arrest in S phase without leading to apoptosis in HBECs as evidenced by TUNEL assay, COMET assay and DNA content assay. CSE stimulated NF-κB -DNA binding activity and up-regulated Bcl-XL protein in HBECs. Inhibition of NF-κB by the pharmacologic inhibitor curcumin (20 μM) or suppression of p65 by siRNA resulted in a significant increase in cell death in response to cigarette smoke exposure. Furthermore, cells lacking p65 were incapable of forming cellular colonies when these cells were exposed to CSE, while they behaved normally in the regular culture medium. The current study demonstrates that CSE activates NF-κB and up-regulates Bcl-XL through NF-kB activation in HBECs, and that CSE induces cell death in cells lacking p65. These results suggest that activation of NF-κB regulates cell survival following DNA damage by cigarette smoke in human bronchial epithelial cells.
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DOI：
10.1152/ajplung.1998.274.4.l591
发表时间：
1998-04-01
影响因子：
4.9
作者：
Carnevali, S;Nakamura, Y;Rennard, SI
通讯作者：
Rennard, SI
影响因子：
8
作者：
He, GG;Siddik, ZH;Kuang, J
通讯作者：
Kuang, J
影响因子：
5.6
作者：
Kim, JA;Kim, DK;Lee, YM
通讯作者：
Lee, YM
影响因子：
2.1
作者：
BECKMANN, JD;TAKIZAWA, H;RENNARD, SI
通讯作者：
RENNARD, SI
影响因子：
4.8
作者：
Franek, WR;Horowitz, S;Mantell, LL
通讯作者：
Mantell, LL