期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 50, 期 -, 页码 29-37出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2014.01.022
关键词
Vascular inflammation; Subendothelial resistin; Fractalkine; MCP-1; TLR4
资金
- Romanian National Authority for Scientific Research
- CNCS-UEFISCDI [PN-II-IDPCE-2011-3-0928]
- CARDIOPRO [143ERDF]
- RTDI for Competitiveness
- Romanian Academy
The cytokine resistin and the chemokine fractalkine (FKN) were found at increased levels in human atherosclerotic plaque, in the subendothelium, but their role in this location still needs to be characterized. Recently, high local resistin in the arterial vessel wall was shown to contribute to an enhanced accumulation of macrophages by mechanisms that need to be clarified. Our recent data showed that resistin activated smooth muscle cells (SMC) by up-regulating FKN and MCP-1 expression and monocyte chemotaxis by activating toll-like receptor 4 (TLR4) and Gi/o proteins. Since in the vessel wall both endothelial cells (EC) and SMC respond to cytokines and promote atherosclerosis, we questioned whether subendothelial resistin (sR) has a role in vascular cells cross-talk leading to enhanced monocyte transmigration and we investigated the mechanisms involved. To this purpose we used an in vitro system of co-cultured SMC and EC activated by SR and we analyzed monocyte transmigration. Our results indicated that: (1) SR enhanced monocyte transmigration in EC/SMC system compared to EC cultured alone; (2) SR activated TLR4 and Gi/o signaling in EC/SMC system and induced the secretion of more FM and MCP-1 compared to EC cultured alone and used both chemokines to specifically recruit monocytes by CX3CR1 and CCR2 receptors. Moreover, FKN produced by resistin in EC/SMC system, by acting on CX3CR1 on EC/SMC specifically contributes to MCP-1 secretibn in the system and to the enhanced monocyte transmigration. Our study indicates new possible targets for therapy to reduce resistin-dependent enhanced macrophage infiltration in the atherosclerotic arterial wall. (C) 2014 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据