CCN1 secretion induced by cigarette smoking extracts augments IL-8 release from bronchial epithelial cells.
CCN1 secretion induced by cigarette smoking extracts augments IL-8 release from bronchial epithelial cells.
复制标题
DOI：
10.1371/journal.pone.0068199
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Moon HG;Zheng Y;An CH;Kim YK;Jin Y
炎症参与许多与香烟烟雾（CS）相关的疾病，包括慢性阻塞性肺疾病（COPD）。肺上皮细胞释放的IL-8在CS诱导的肺部炎症中起重要作用。CS和香烟烟雾提取物（CSE）均诱导IL-8分泌，随后，IL-8将炎性细胞募集到肺实质中。然而，CSE触发IL-8释放的分子和细胞机制仍不完全清楚。在这项研究中，我们确定了一种新的细胞外基质（ECM）分子，CCN 1，它介导CSE诱导肺上皮细胞分泌IL-8。我们首次发现CS和CSE在体内和体外上调肺上皮细胞中CCN 1的表达和分泌。CSE通过诱导活性氧（ROS）和内质网（ER）应激上调CCN 1。p38 MAPK和JNK激活也被发现介导CSE诱导的CCN 1的信号通路。CCN 1通过高尔基体和膜通道受体水通道蛋白4分泌到ECM中。CSE暴露后，升高的ECM CCN 1通过自分泌或旁分泌方式发挥作用。重要的是，CCN 1激活Wnt途径受体LRP 6，随后刺激Wnt途径组分Dv 12并触发β-连环蛋白从细胞膜易位至细胞质溶胶和细胞核。Wnt通路抑制剂的处理抑制CCN 1诱导的肺上皮细胞的IL-8分泌。总之，CSE通过诱导ROS和ER应激增加肺上皮细胞中CCN 1的表达和分泌。增加的ECM CCN 1通过激活Wnt途径导致IL-8释放增加。
Inflammation involves in many cigarette smoke (CS) related diseases including the chronic obstructive pulmonary disease (COPD). Lung epithelial cell released IL-8 plays a crucial role in CS induced lung inflammation. CS and cigarette smoke extracts (CSE) both induce IL-8 secretion and subsequently, IL-8 recruits inflammatory cells into the lung parenchyma. However, the molecular and cellular mechanisms by which CSE triggers IL-8 release remain not completely understood. In this study, we identified a novel extracellular matrix (ECM) molecule, CCN1, which mediated CSE induced IL-8 secretion by lung epithelial cells. We first found that CS and CSE up-regulated CCN1 expression and secretion in lung epithelial cells in vivo and in vitro. CSE up-regulated CCN1 via induction of reactive oxygen spices (ROS) and endoplasmic reticulum (ER) stress. p38 MAPK and JNK activation were also found to mediate the signal pathways in CSE induced CCN1. CCN1 was secreted into ECM via Golgi and membrane channel receptor aquaporin4. After CSE exposure, elevated ECM CCN1 functioned via an autocrine or paracrine manner. Importantly, CCN1 activated Wnt pathway receptor LRP6, subsequently stimulated Wnt pathway component Dvl2 and triggered beta-catenin translocation from cell membrane to cytosol and nucleus. Treatment of Wnt pathway inhibitor suppressed CCN1 induced IL-8 secretion from lung epithelial cells. Taken together, CSE increased CCN1 expression and secretion in lung epithelial cells via induction of ROS and ER stress. Increased ECM CCN1 resulted in augmented IL-8 release through the activation of Wnt pathway.
登录
查看更多内容
DOI：
10.1152/ajplung.00102.2012
发表时间：
2012-11-01
影响因子：
4.9
作者：
An, Chang Hyeok;Wang, Xiao Mei;Choi, Augustine M. K.
通讯作者：
Choi, Augustine M. K.
影响因子：
4.8
作者：
Leu, SJ;Lam, SCT;Lau, LF
通讯作者：
Lau, LF
影响因子：
24.3
作者：
Crooks, SW;Bayley, DL;Stockley, RA
通讯作者：
Stockley, RA
DOI：
10.1164/ajrccm.150.3.8087340
发表时间：
1994-09-01
影响因子：
24.7
作者：
MCCREA, KA;ENSOR, JE;HASDAY, JD
通讯作者：
HASDAY, JD
DOI：
10.1164/ajrccm/144.1.17
发表时间：
1991-07-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
SHERRILL, DL;LEBOWITZ, MD;BURROWS, B
通讯作者：
BURROWS, B