Nitric oxide/cGMP signalling induces Escherichia coli K1 receptor expression and modulates the permeability in human brain endothelial cell monolayers during invasion.
Nitric oxide/cGMP signalling induces Escherichia coli K1 receptor expression and modulates the permeability in human brain endothelial cell monolayers during invasion.
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DOI：
10.1111/j.1462-5822.2009.01379.x
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发表时间：
2010-01
影响因子：
3.4
通讯作者：
Prasadarao NV
中科院分区：
文献类型：
--
作者：
Mittal R;Prasadarao NV
外膜蛋白A（OmpA）介导大肠杆菌K1侵入人麸皮微血管内皮细胞（HBMEC），导致HBMEC单层渗漏。尽管一氧化氮（NO）对内皮细胞紧密连接完整性有影响，但其在E。coli诱导的HBMEC单层渗透性定义不明确。在这里，我们证明了E。大肠杆菌侵袭HBMEC通过增加诱导型一氧化氮合酶（iNOS）表达刺激NO产生。NO产生剂可增强OmpA+ E的侵袭能力。coli，从而增加HBMEC的通透性。OmpA+ E。大肠杆菌诱导的NO产生导致cGMP产生增加，并触发OmpA受体Ec-gp 96的表达。用iNOS抑制剂预处理HBMEC，或将siRNA引入iNOS，但不引入eNOS或cGMP抑制剂，可消除E.大肠杆菌诱导表达Ec-gp 96。在HBMEC中过表达C-末端截短的Ec-gp 96可抑制NO的产生及其下游效应物cGMP的产生，从而抑制OmpA+ E的侵袭。杆菌NO/cGMP的产生也激活PKC-α，这是以前显示参与HBMEC单层渗漏。这些结果表明，NO/cGMP信号通路在OmpA+ E中起着新的作用。大肠杆菌通过增强Ec-gp 96的表面表达来抑制HBMEC的侵袭。
Escherichia coli K1 invasion of human bran microvascular endothelial cells (HBMEC) mediated by outer membrane protein A (OmpA) results in the leakage of HBMEC monolayers. Despite the influence of nitric oxide (NO) in endothelial cell tight junction integrity, its role in E. coli induced HBMEC monolayer permeability is poorly defined. Here, we demonstrate that E. coli invasion of HBMEC stimulates NO production by increasing the inducible nitric oxide synthase (iNOS) expression. Exposure to NO producing agents enhanced the invasion of OmpA+ E. coli and thereby increased the permeability of HBMEC. OmpA+ E. coli-induced NO production lead to increased generation of cGMP and triggered the expression of OmpA receptor, Ec-gp96 in HBMEC. Pre-treatment of HBMEC with iNOS inhibitors or by introducing siRNA to iNOS, but not to eNOS or cGMP inhibitors abrogated the E. coli-induced expression of Ec-gp96. Overexpression of the C-terminal truncated Ec-gp96 in HBMEC prevented NO production and its downstream effector, cGMP generation and consequently, the invasion of OmpA+ E. coli. NO/cGMP production also activates PKC-α, which is previously shown to be involved in HBMEC monolayer leakage. These results indicate that NO/cGMP signaling pathway plays a novel role in OmpA+ E. coli invasion of HBMEC by enhancing the surface expression of Ec-gp96.
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影响因子：
4.8
作者：
Hou, YL;Lascola, J;Browning, DD
通讯作者：
Browning, DD
影响因子：
56.9
作者：
Coureuil, Mathieu;Mikaty, Guillain;Nassif, Xavier
通讯作者：
Nassif, Xavier
影响因子：
3.8
作者：
Khan, SA;Strijbos, PJLM;Maskell, DJ
通讯作者：
Maskell, DJ
影响因子：
3.4
作者：
Maruvada R;Argon Y;Prasadarao NV
通讯作者：
Prasadarao NV
DOI：
10.1165/ajrcmb.25.5.4487
发表时间：
2001-11-01
影响因子：
6.4
作者：
Chan, ED;Chan, J;Schluger, NW
通讯作者：
Schluger, NW