The transcriptional factor PREB mediates MCP-1 transcription induced by cytokines in human vascular endothelial cells
The transcriptional factor PREB mediates MCP-1 transcription induced by cytokines in human vascular endothelial cells
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DOI：
10.1016/j.atherosclerosis.2009.03.051
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发表时间：
2009-11-01
期刊：
影响因子：
5.3
通讯作者：
Ishida, Toshihiko
中科院分区：
文献类型：
--
作者：
Murao, Koji;Imachi, Hitomi;Ishida, Toshihiko
目的：催乳素调控元件结合蛋白（PREB）是调节大鼠垂体前叶催乳素启动子活性的转录因子。它不仅在垂体前叶中表达，也在心血管系统中表达，包括人脐血管内皮细胞（HUVECs）。单核细胞趋化蛋白-1 （MCP-1）是单核细胞的主要趋化因子，也是启动动脉粥样硬化炎症过程的关键因子。MCP-1在HUVECs中表达，以响应几种不同的刺激，包括白细胞介素(IL)-1 β和肿瘤坏死因子(TNF)- α。方法和结果：MCP-1的表达受IL-1 β、tnf - α和细胞因子诱导的PREB表达的调控。相反，使用表达PREB的腺病毒过表达PREB可增加HUVECs中MCP-1的表达。此外，在MCP-1启动子控制下，PREB诱导荧光素酶报告蛋白的表达。EMSA表明，PREB的转录作用是通过与MCP-1启动子的PREB应答顺式元件结合而介导的。最后，我们使用siRNA抑制了PREB在HUVECs中的表达，并证明了PREB表达的下调减弱了IL-1 β和tnf - α对MCP-1表达的影响。结论：综上所述，我们的研究结果表明，PREB可以作为MCP-1启动子的转录调节因子，响应细胞因子。2009爱思唯尔爱尔兰有限公司版权所有。
Objective: The prolactin regulatory element binding (PREB) protein is a transcriptional factor that regulates prolactin promoter activity in rat anterior pituitary. It is expressed not only in the anterior pituitary but also in the cardiovascular system, including in human umbilical vascular endothelial cells (HUVECs). Monocyte chemoattractant protein-1 (MCP-1) is a major chemotactic factor for monocytes and a key factor initiating the inflammatory process of atherogenesis. MCP-1 is expressed in HUVECs in response to several different stimuli, including interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha.Methods and results: MCP-1 expression was regulated by IL-1 beta and TNF-alpha and cytokine-induced PREB expression. Conversely, over-expression of PREB using a PREB-expressing adenovirus increased MCP-1 expression in HUVECs. In addition, PREB induced the expression of the luciferase reporter protein under the MCP-1 promoter control. EMSA showed that the transcriptional effect of PREB was mediated by its binding to the PREB-responsive cis-element of the MCP-1 promoter. Finally, we used siRNA to inhibit PREB expression in HUVECs and demonstrated that knockdown of PREB expression attenuated the effects of IL-1 beta and TNF-alpha on MCP-1 expression.Conclusions: In summary, our findings show that PREB can function as a transcriptional regulator of the MCP-1 promoter in response to cytokines. (C) 2009 Elsevier Ireland Ltd. All rights reserved.