PMID- 12067898
OWN - NLM
STAT- MEDLINE
DCOM- 20020703
LR  - 20220414
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 22
IP  - 6
DP  - 2002 Jun 1
TI  - Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 
      production in human smooth muscle cells by differential activation of nuclear 
      factor-kappaB and activator protein-1.
PG  - 914-20
AB  - Inflammatory response and chemotaxis of vascular wall cells play an important 
      pathogenic role in the development of atherosclerosis. Monocyte chemoattractant 
      protein-1 (MCP-1) is a potent chemoattractant for monocytes. Besides the 
      induction of monocyte recruitment, it has been suggested that MCP-1 may directly 
      activate smooth muscle cells. We investigated whether MCP-1 affects the 
      proliferation and cytokine production of human vascular smooth muscle cells 
      (VSMCs) and determined the underlying signal transduction pathways. Stimulation 
      of VSMCs with MCP-1 induced proliferation and resulted in a concentration- and 
      time-dependent release of the proinflammatory cytokine interleukin-6 (IL-6). 
      Pretreatment with pertussis toxin, GF109203X, and pyrrolidine dithiocarbamate 
      inhibited MCP-1-dependent IL-6 release, suggesting the involvement of G(i) 
      proteins, protein kinase C, and nuclear factor-kappaB (NF-kappaB). MCP-1 also 
      induced extracellular signal-regulated kinase, which, along with IL-6 release, 
      was inhibited by pertussis toxin. PD98059 prevented MCP-1-induced extracellular 
      signal-regulated kinase activation and cell proliferation. MCP-1 stimulated the 
      binding activity of NF-kappaB and of activator protein-1 (AP-1). As demonstrated 
      by cis element double-stranded (decoy) oligodeoxynucleotides, NF-kappaB was 
      involved in IL-6 release by MCP-1, whereas proliferation was dependent on AP-1. 
      The results clearly demonstrate that MCP-1 induces differential activation of 
      NF-kappaB and AP-1 in VSMCs. Thus, our data propose a new mechanism for the 
      proatherogenic effect of MCP-1.
FAU - Viedt, Christiane
AU  - Viedt C
AD  - Innere Medizin III, Universitat Heidelberg, Germany.
FAU - Vogel, Judith
AU  - Vogel J
FAU - Athanasiou, Thomas
AU  - Athanasiou T
FAU - Shen, Weili
AU  - Shen W
FAU - Orth, Stephan R
AU  - Orth SR
FAU - Kubler, Wolfgang
AU  - Kubler W
FAU - Kreuzer, Jorg
AU  - Kreuzer J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Growth Substances)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cell Division/physiology
MH  - Chemokine CCL2/*physiology
MH  - Coronary Artery Bypass
MH  - Enzyme Activation/physiology
MH  - Growth Substances/*physiology
MH  - Humans
MH  - Inflammation/metabolism
MH  - Interleukin-6/*biosynthesis/metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Muscle, Smooth, Vascular/*cytology/*metabolism
MH  - NF-kappa B/*physiology
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/biosynthesis
MH  - Recombinant Proteins/metabolism
MH  - Saphenous Vein/cytology
MH  - Transcription Factor AP-1/*physiology
EDAT- 2002/06/18 10:00
MHDA- 2002/07/04 10:01
CRDT- 2002/06/18 10:00
PHST- 2002/06/18 10:00 [pubmed]
PHST- 2002/07/04 10:01 [medline]
PHST- 2002/06/18 10:00 [entrez]
AID - 10.1161/01.atv.0000019009.73586.7f [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2002 Jun 1;22(6):914-20. doi: 
      10.1161/01.atv.0000019009.73586.7f.