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The transcriptional factor PREB mediates MCP-1 transcription induced by cytokines in human vascular endothelial cells.

Abstract：

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)-1beta and tumor necrosis factor (TNF)-alpha. METHODS AND RESULTS:MCP-1 expression was regulated by IL-1beta 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-1beta 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.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Murao K,Imachi H,Yu X,Muraoka T,Hosami N,Dobashi H,Ishida T

doi

10.1016/j.atherosclerosis.2009.03.051

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

45-50

issue

1

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(09)00265-2

journal_volume

207

pub_type

杂志文章

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