Lipopolysaccharide modifies amiloride-sensitive Na+ transport processes across human airway cells: role of mitogen-activated protein kinases ERK 1/2 and 5.
Lipopolysaccharide modifies amiloride-sensitive Na+ transport processes across human airway cells: role of mitogen-activated protein kinases ERK 1/2 and 5.
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脂多糖修饰了跨人类气道细胞的艾米洛德敏感的Na+转运过程：有丝分裂原激活的蛋白激酶ERK 1/2和5的作用。
DOI：
10.1007/s00424-009-0717-4
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发表时间：
2010-02
影响因子：
4.5
通讯作者：
Dockrell, M. E. C.
中科院分区：
文献类型：
--
作者：
Baines, D. L.;Albert, A. P.;Hazell, M. J.;Gambling, L.;Woollhead, A. M.;Dockrell, M. E. C.
细菌脂多糖（LPS）是促炎信号通路的有效诱导剂，通过激活核因子κB （NF-κB）和丝裂原活化蛋白激酶（MAPK），导致控制肺液稳态的过程发生变化，并参与肺部疾病的发病机制。在人类H441气道上皮细胞,细胞孵化15µg毫升−1 LPS引起显著减少amiloride-sensitive我从15±2到8±2 scµ厘米−2 (p = 0.01, n = 13)和转变IC50阿米洛利的电流从6.8×10 7−6.4×10−6 M .这种效应与减少的活动5 pS,高度Na +选择性,amiloride-sensitive < 1µM通道(HSC)和增加的活动∼18 pS,非选择性,在根尖膜上有amilorides敏感的bbb10µM阳离子通道（NSC）。LPS降低αENaC mRNA和蛋白丰度，提示LPS抑制αENaC基因表达。这与HSC活性降低相关，表明这些通道（而非NSCs）至少由αENaC蛋白组成。LPS可提高H441细胞NF-κB DNA结合活性和细胞外信号相关激酶（ERK）1/2的磷酸化水平，降低ERK5的磷酸化水平。PD98059（20µM）预处理单层膜抑制ERK1/2磷酸化，促进ERK5磷酸化，增加αENaC蛋白丰度，逆转LPS对I sc的影响和阿米罗利敏感性的转变。NF-κB活化抑制剂无效果。综上所述，我们的数据表明，LPS通过ERK信号通路减少αENaC转录，降低H441气道上皮细胞中HSC/ENaC通道的丰度、活性和经上皮Na+转运。
Bacterial lipopolysaccharides (LPS) are potent inducers of proinflammatory signaling pathways via the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), causing changes in the processes that control lung fluid homeostasis and contributing to the pathogenesis of lung disease. In human H441 airway epithelial cells, incubation of cells with 15 µg ml−1 LPS caused a significant reduction in amiloride-sensitive I sc from 15 ± 2 to 8 ± 2 µA cm−2 (p = 0.01, n = 13) and a shift in IC50 amiloride of currents from 6.8 × 10−7 to 6.4 × 10−6 M. This effect was associated with a decrease in the activity of 5 pS, highly Na+ selective, amiloride-sensitive <1 µM channels (HSC) and an increase in the activity of ∼18 pS, nonselective, amiloride-sensitive >10 µM cation channels (NSC) in the apical membrane. LPS decreased αENaC mRNA and protein abundance, inferring that LPS inhibited αENaC gene expression. This correlated with the decrease in HSC activity, indicating that these channels, but not NSCs, were comprised of at least αENaC protein. LPS increased NF-κB DNA binding activity and phosphorylation of extracellular signal-related kinase (ERK)1/2, but decreased phosphorylation of ERK5 in H441 cells. Pretreatment of monolayers with PD98059 (20 µM) inhibited ERK1/2 phosphorylation, promoted phosphorylation of ERK5, increased αENaC protein abundance, and reversed the effect of LPS on I sc and the shift in amiloride sensitivity. Inhibitors of NF-κB activation were without effect. Taken together, our data indicate that LPS acts via ERK signaling pathways to decrease αENaC transcription, reducing HSC/ENaC channel abundance, activity, and transepithelial Na+ transport in H441 airway epithelial cells.
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DOI：
10.1152/ajplung.00511.2005
发表时间：
2006-12-01
影响因子：
4.9
作者：
Dagenais, Andre;Frechette, Rosalie;Berthiaume, Yves
通讯作者：
Berthiaume, Yves
DOI：
10.1073/pnas.0600855103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Johnson, MD;Bao, HF;Eaton, DC
通讯作者：
Eaton, DC
DOI：
10.1152/ajplung.1999.276.6.l1046
发表时间：
1999-06-01
影响因子：
4.9
作者：
Jain, L;Chen, XJ;Eaton, DC
通讯作者：
Eaton, DC
DOI：
10.1085/jgp.112.4.423
发表时间：
1998-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Fyfe GK;Canessa CM
通讯作者：
Canessa CM
DOI：
10.1152/ajplung.00085.2001
发表时间：
2002-04-01
影响因子：
4.9
作者：
Itani, OA;Auerbach, SD;Thomas, CP
通讯作者：
Thomas, CP