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学科主题: 基础医学
题名:
Homocysteine mediated expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human monocytes
作者: Zeng, XK; Dai, J; Remick, DG; Wang, X
关键词: homocysteine ; monocytes ; atherosclerosis ; monocyte chemoattractant protein-1 ; interleukin-8
刊名: CIRCULATION RESEARCH
发表日期: 2003-08-22
DOI: 10.1161/01.RES.0000087642.01082.E4
卷: 93, 期:4, 页:311-320
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Hematology
关键词[WOS]: ENDOTHELIAL-CELL INJURY ; SMOOTH-MUSCLE-CELLS ; NF-KAPPA-B ; RISK FACTOR ; PLASMA HOMOCYST(E)INE ; ATHEROMATOUS PLAQUES ; VASCULAR-DISEASE ; OXIDATIVE STRESS ; OXIDANT STRESS ; T-LYMPHOCYTES
英文摘要:

Homocysteine (Hcy) is an independent risk factor for cardiovascular disease. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are major chemokines for leukocyte trafficking and have been identified in atheromatous plaques. MCP-1 and IL-8 have been found to express mainly by macrophages in human lesion. We undertook this study to determine whether Hcy could induce the secretion of chemokines from human monocytes and, if so, to explore the mediating mechanism. We found that clinically relevant levels of Hcy (10 to 1000 mumol/L) increased the protein secretion and mRNA expression as well as activity of MCP-1 and IL-8 in cultured primary human monocytes. These effects of Hcy were primarily mediated by reactive oxygen species (ROS) through NAD(P) H oxidase, because Hcy could upregulate the production of ROS and the inhibitors of protein kinase C, calmodulin, free radical scavengers, or NAD(P) H oxidase abolished Hcy-induced ROS production and MCP-1 and IL-8 secretion in these cells. Furthermore, the inhibitors of mitogen-activated protein kinase (p38 and extracellular signal-regulated kinase 1/2) and nuclear factor-kappaB or the activator of peroxisome proliferator-activated receptor gamma(PPARgamma) significantly decreased Hcy-induced MCP-1 and IL-8 secretion in these cells. These data indicate that pathophysiological levels of Hcy can alter human monocyte function by upregulating MCP-1 and IL-8 expression and secretion via enhanced formation of intracellular ROS originated from NAD(P) H oxidase source via calmodulin or protein kinase C signaling pathways and that Hcy-induced ROS subsequently activates mitogen-activated protein kinase (p38 and ERK1/2) and nuclear factor-kappaB in a PPARgamma activator-sensitive manner. Thus, activation of PPARgamma may become a therapeutic target for preventing Hcy-induced proatherogenic effects.

语种: 英语
WOS记录号: WOS:000184882200007
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58896
Appears in Collections:基础医学院_生理学与病理生理学系_期刊论文

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作者单位: 1.Peking Univ, Basic Med Coll, Dept Physiol, Beijing 100083, Peoples R China
2.Peking Univ, Basic Med Coll, Educ Minist Mol Cardiol, Reference Lab, Beijing 100871, Peoples R China
3.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100871, Peoples R China
4.Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA

Recommended Citation:
Zeng, XK,Dai, J,Remick, DG,et al. Homocysteine mediated expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human monocytes[J]. CIRCULATION RESEARCH,2003,93(4):311-320.
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