Functional characterization of S100A8 and S100A9 in altering monolayer permeability of human umbilical endothelial cells.
Functional characterization of S100A8 and S100A9 in altering monolayer permeability of human umbilical endothelial cells.
复制标题
DOI：
10.1371/journal.pone.0090472
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Huang Q
中科院分区：
文献类型：
--
作者：
Wang L;Luo H;Chen X;Jiang Y;Huang Q
S100 A8、S100 A9和S100 A8/A9复合物是重要的内源性损伤相关分子模式（DAMP）蛋白。但S100 A8、S100 A9和S100 A8/A9在心血管疾病中的病理生理作用尚不完全清楚。本研究以培养的人脐静脉内皮细胞（HUVECs）为模型，分别检测了同源S100 A8、S100 A9及其复合物S100 A8/A9对内皮屏障功能的影响。应用TLR 4抑制剂和抗TLR 4阻断抗体观察TLR 4和TLR 4的参与。利用特异性抑制剂阐明S100 A8/A9诱导的内皮细胞反应中MAPK的不同亚型。在无Ca ~（2+）或有梯度剂量Ca ~（2+）存在的情况下检测到钙依赖性。结果表明，S100 A8、S100 A9和S100 A8/A9均能诱导HUVECs内F-actin和ZO-1结构紊乱，并呈剂量和时间依赖性地诱导HUVECs单层通透性增加。S100 A8、S100 A9和S100 A8/A9对内皮屏障功能的影响依赖于通过受体TLR 4和ERK激活p38和ERK 1/2信号通路。最重要的是，我们揭示了S100 A8对TLR 4和S100 A9对HUVECs中TLR 4的偏好。结果还显示，在S100 A8和S100 A9诱发的内皮反应中的钙依赖性，表明对S100 A8或A9二聚体形成的钙依赖性可能是这种内皮功能改变的先决条件。
S100A8, S100A9 and S100A8/A9 complexes have been known as important endogenous damage-associated molecular pattern (DAMP) proteins. But the pathophysiological roles of S100A8, S100A9 and S100A8/A9 in cardiovascular diseases are incompletely explained. In this present study, the effects of homo S100A8, S100A9 and their hetero-complex S100A8/A9 on endothelial barrier function were tested respectively in cultured human umbilical venous endothelial cells (HUVECs). The involvement of TLR4 and RAGE were observed by using inhibitor of TLR4 and blocking antibody of RAGE. The clarification of different MAPK subtypes in S100A8/A9-induced endothelial response was implemented by using specific inhibitors. The calcium-dependency was detected in the absence of Ca2+ or in the presence of gradient-dose Ca2+. The results showed that S100A8, S100A9 and S100A8/A9 could induce F-actin and ZO-1 disorganization in HUVECs and evoked the increases of HUVEC monolayer permeability in a dose- and time-dependent manner. The effects of S100A8, S100A9 and S100A8/A9 on endothelial barrier function depended on the activation of p38 and ERK1/2 signal pathways through receptors TLR4 and RAGE. Most importantly, we revealed the preference of S100A8 on TLR4 and S100A9 on RAGE in HUVECs. The results also showed the calcium dependency in S100A8- and S100A9-evoked endothelial response, indicating that calcium dependency on formation of S100A8 or A9 dimmers might be the prerequisite for this endothelial functional alteration.
登录
查看更多内容
影响因子：
9.3
作者：
Ehlermann, Philipp;Eggers, Kai;Remppis, Andrew
通讯作者：
Remppis, Andrew
影响因子：
16.8
作者：
Roth, J;Vogl, T;Sunderkötter, C
通讯作者：
Sunderkötter, C
DOI：
10.1016/j.bbamcr.2005.03.007
发表时间：
2005-06-30
影响因子：
5.1
作者：
Mukherjee, TK;Mukhopadhyay, S;Hoidal, JR
通讯作者：
Hoidal, JR
影响因子：
4.8
作者：
Hunter, MJ;Chazin, WJ
通讯作者：
Chazin, WJ
影响因子：
37.8
作者：
Shimizu K;Libby P;Rocha VZ;Folco EJ;Shubiki R;Grabie N;Jang S;Lichtman AH;Shimizu A;Hogg N;Simon DI;Mitchell RN;Croce K
通讯作者：
Croce K