PMID- 12881478
OWN - NLM
STAT- MEDLINE
DCOM- 20031015
LR  - 20220224
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 93
IP  - 4
DP  - 2003 Aug 22
TI  - Homocysteine mediated expression and secretion of monocyte chemoattractant 
      protein-1 and interleukin-8 in human monocytes.
PG  - 311-20
AB  - 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 
      micromol/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.
FAU - Zeng, Xiaokun
AU  - Zeng X
AD  - Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 
      People's Republic of China.
FAU - Dai, Jing
AU  - Dai J
FAU - Remick, Daniel G
AU  - Remick DG
FAU - Wang, Xian
AU  - Wang X
LA  - eng
GR  - GM 50401/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030724
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromans)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Indoles)
RN  - 0 (Interleukin-8)
RN  - 0 (Naphthalenes)
RN  - 0 (Onium Compounds)
RN  - 0 (Pyridines)
RN  - 0 (Pyrrolidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sulfonamides)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Thiocarbamates)
RN  - 0 (Tyrphostins)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - 65595-90-6 (W 7)
RN  - 6HJ411TU98 (diphenyleneiodonium)
RN  - DH2M523P0H (Genistein)
RN  - I271P23G24 (calphostin C)
RN  - I66ZZ0ZN0E (Troglitazone)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - U8QXS1WU8G (ciglitazone)
RN  - W9A0B5E78O (Ro 31-8220)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
CIN - Circ Res. 2003 Aug 22;93(4):271-3. PMID: 12933697
MH  - Antioxidants/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chromans/pharmacology
MH  - Dimethyl Sulfoxide/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Genistein/pharmacology
MH  - Homocysteine/*pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Indoles/pharmacology
MH  - Interleukin-8/genetics/*metabolism
MH  - Monocytes/cytology/*drug effects/metabolism
MH  - Naphthalenes/pharmacology
MH  - Onium Compounds/pharmacology
MH  - Pyridines/pharmacology
MH  - Pyrrolidines/pharmacology
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Sulfonamides/pharmacology
MH  - Thiazoles/pharmacology
MH  - *Thiazolidinediones
MH  - Thiocarbamates/pharmacology
MH  - Time Factors
MH  - Troglitazone
MH  - Tyrphostins/pharmacology
EDAT- 2003/07/26 05:00
MHDA- 2003/10/16 05:00
CRDT- 2003/07/26 05:00
PHST- 2003/07/26 05:00 [pubmed]
PHST- 2003/10/16 05:00 [medline]
PHST- 2003/07/26 05:00 [entrez]
AID - 01.RES.0000087642.01082.E4 [pii]
AID - 10.1161/01.RES.0000087642.01082.E4 [doi]
PST - ppublish
SO  - Circ Res. 2003 Aug 22;93(4):311-20. doi: 10.1161/01.RES.0000087642.01082.E4. Epub 
      2003 Jul 24.