PMID- 10669634
OWN - NLM
STAT- MEDLINE
DCOM- 20000303
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 20
IP  - 2
DP  - 2000 Feb
TI  - Convergence of redox-sensitive and mitogen-activated protein kinase signaling 
      pathways in tumor necrosis factor-alpha-mediated monocyte chemoattractant 
      protein-1 induction in vascular smooth muscle cells.
PG  - 385-91
AB  - Monocyte chemoattractant protein-1 (MCP-1) is an important component of the 
      inflammatory response of the vessel wall and has been shown to be regulated by 
      cytokines, such as tumor necrosis factor-alpha (TNF-alpha). However, the precise 
      signaling pathways leading to MCP-1 induction have not been fully elucidated in 
      vascular smooth muscle cells (VSMCs). Cytokine signal transduction involves 
      protein kinases as well as reactive oxygen species (ROS). The relation between 
      these 2 factors is not clear. In this study, we show that TNF-alpha induces a 
      parallel phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) 
      and p38 mitogen-activated protein kinase (p38MAPK) and increases MCP-1 mRNA 
      expression in cultured VSMCs. Inhibition of ERK1/2 but not p38MAPK caused a 
      partial attenuation of MCP-1 induction (43+/-10% inhibition). Incubation of VSMCs 
      with multiple antioxidants (diphenylene iodonium, liposomal superoxide dismutase, 
      catalase, N-acetylcysteine, dimethylthiourea, and pyrrolidine dithiocarbamate) 
      had no effect on TNF-alpha-mediated MCP-1 upregulation. However, simultaneous 
      blockade of the ERK1/2 and ROS pathways by using PD098059 combined with 
      diphenylene iodonium or N-acetylcysteine potently enhanced the ability of MAPK 
      kinase inhibitors to abrogate MCP-1 mRNA expression (100+/-2% inhibition). Thus, 
      parallel ROS-dependent and ERK1/2-dependent pathways converge to regulate 
      TNF-alpha-induced MCP-1 gene expression in VSMCs. These data unmask a complex but 
      organized integration of ROS and protein kinases that mediates cytokine-induced 
      vascular inflammatory gene expression.
FAU - De Keulenaer, G W
AU  - De Keulenaer GW
AD  - Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, 
      USA.
FAU - Ushio-Fukai, M
AU  - Ushio-Fukai M
FAU - Yin, Q
AU  - Yin Q
FAU - Chung, A B
AU  - Chung AB
FAU - Lyons, P R
AU  - Lyons PR
FAU - Ishizaka, N
AU  - Ishizaka N
FAU - Rengarajan, K
AU  - Rengarajan K
FAU - Taylor, W R
AU  - Taylor WR
FAU - Alexander, R W
AU  - Alexander RW
FAU - Griendling, K K
AU  - Griendling KK
LA  - eng
GR  - HL-58863/HL/NHLBI 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.
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Chemokine CCL2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - Muscle, Smooth, Vascular/cytology/drug effects/*metabolism
MH  - Oxidation-Reduction
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology/*physiology
MH  - Up-Regulation
EDAT- 2000/02/17 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/17 09:00
PHST- 2000/02/17 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/17 09:00 [entrez]
AID - 10.1161/01.atv.20.2.385 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):385-91. doi: 
      10.1161/01.atv.20.2.385.