P. aeruginosa lipopolysaccharide-induced MUC5AC and CLCA3 expression is partly through Duox1 in vitro and in vivo.
P. aeruginosa lipopolysaccharide-induced MUC5AC and CLCA3 expression is partly through Duox1 in vitro and in vivo.
复制标题
DOI：
10.1371/journal.pone.0063945
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Li W;Yan F;Zhou H;Lin X;Wu Y;Chen C;Zhou N;Chen Z;Li JD;Shen H
我们以前发现，活性氧（ROS）参与了铜绿假单胞菌脂多糖（PA-LPS）诱导的气道上皮细胞MUC 5AC。双氧化酶1（Duox 1）是NADPH氧化酶（Nox）的一个成员，已知其负责呼吸道上皮细胞中ROS的产生。我们的目的是阐明Duox 1是否也参与PA-LPS诱导的MUC 5AC和钙依赖性氯离子通道3（Clca 3），这是另一种公认的杯状细胞增生和粘液分泌过多的标志物。 在A549细胞、原代小鼠气管上皮细胞（mTECS）和小鼠肺组织中检测PA-LPS诱导的Duox 1 mRNA水平。采用Nox抑制剂氯化二苯碘铵（DPI）和Duox 1 siRNA研究Duox 1是否参与了PA LPS诱导的MUC 5AC和Clca 3表达。在A549细胞、原代mTECs和小鼠肺组织中，PA-LPS诱导Duox 1。DPI可显著抑制PA-LPS诱导的小鼠原代气管上皮细胞和肺组织Duox 1、Muc 5ac和Clca 3表达上调。Duox 1基因的敲除可通过ROS-TGF-α级联反应抑制PA-LPS诱导的A549细胞MUC 5AC表达。此外，DPI显着抑制PA-LPS诱导的小鼠肺中炎症细胞积聚的增加。我们首次证明PA-LPS诱导的MUC 5AC和Clca 3表达部分通过Duox 1，并为Duox 1作为治疗粘蛋白过量产生疾病的潜在靶点提供了支持性证据。
We have previously found that reactive oxygen species (ROS) are involved in Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) induced MUC5AC in airway epithelial cells. Dual oxidase1 (Duox1), a member of NADPH oxidase(Nox), is known to be responsible for ROS production in respiratory tract epithelial cells. Our aim was to clarify whether Duox1 was also involved in the PA-LPS-induced MUC5AC and calcium dependent chloride channel 3(Clca3), another recognized marker of goblet cell hyperplasia and mucus hyper-production. PA-LPS-induced Duox1 mRNA levels were examined in A549 cells, primary mouse tracheal epithelial cells (mTECS) and lung tissues of mice. Nox inhibitors diphenyleneiodonium chloride (DPI) and Duox1 siRNA were used to investigate whether Duox1 is involved in PA-LPS-induced MUC5AC and Clca3 expression both in vitro and in vivo. Duox1 is induced by PA-LPS in A549 cells, primary mTECs and lung tissues of mice. DPI significantly inhibited PA-LPS-induced up-regulation of Duox1, Muc5ac and Clca3 in primary mouse trachea epithelial cells and lung tissues of mice. Knockdown of Duox1 markedly inhibited PA-LPS-induced MUC5AC expression via a ROS-TGF-α cascade in A549 cells. Furthermore, DPI significantly inhibited PA-LPS-induced increases in inflammatory cells accumulated in mouse lungs. We demonstrate for the first time that PA-LPS-induced MUC5AC and Clca3 expression is partly through Duox1, and provide supportive evidence for Duox1 as a potential target in treatments of mucin over-production diseases.
登录
查看更多内容
DOI：
10.1152/ajplung.00356.2006
发表时间：
2007-05-01
影响因子：
4.9
作者：
Nakanaga, Takashi;Nadel, Jay A.;Shao, Matt X. G.
通讯作者：
Shao, Matt X. G.
影响因子：
4.8
作者：
Lora, JM;Zhang, DM;Fraser, CC
通讯作者：
Fraser, CC
影响因子：
3
作者：
Hovenberg, HW;Davies, JR;Carlstedt, I
通讯作者：
Carlstedt, I
影响因子：
24.3
作者：
Kohri, K;Ueki, IF;Nadel, JA
通讯作者：
Nadel, JA
DOI：
10.1164/ajrccm.165.8.2107068
发表时间：
2002-04-15
影响因子：
24.7
作者：
Hoshino, M;Morita, S;Fujino, M
通讯作者：
Fujino, M