Monocyte chemoattractant protein 1 inhibits growth of rat vascular smooth muscle cells.
The early atherosclerotic lesion is characterized by the migration of inflammatory cells, including monocytes, which may serve as a source of cytokines such as monocyte chemoattractant protein 1 (MCP-1), a homologue of mouse JE. We investigated the effect of MCP-1 on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. In Northern blot analysis, MCP-1/JE transcripts were not observed in unstimulated VSMC, but its expression was clearly observed by exposure to lipopolysaccharide (1 micrograms/ml) for 6 h. Human recombinant MCP-1 inhibited the uptake of [3H]thymidine by VSMC cultured in 0.5% fetal bovine serum (FBS) containing Dulbecco's modified Eagle's medium (DMEM) in a dose-dependent manner. The inhibitory effect of MCP-1 on the growth of VSMC was also confirmed by a change in cell counts. The antiproliferative effect of MCP-1 was significantly blocked in the presence of an anti-MCP-1 antibody. MCP-1-induced inhibition of [3H]thymidine uptake was not affected in the presence of indomethacin (1 micrograms/ml) or NG-monomethyl-L-arginine (0.1 mM), and MCP-1 showed no effect on 6-ketoprostaglandin F1 alpha, guanosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphate syntheses in VSMC. These results indicate that MCP-1 inhibits the proliferation of VSMC in vitro and that its effect is independent of prostaglandin or nitric oxide generation.
Ikeda
U
U
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Okada
K
K
Ishikawa
S
S
Saito
T
T
Kasahara
T
T
Shimada
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D019323:omega-N-Methylarginine
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D015121:6-Ketoprostaglandin F1 alpha; D004247:DNA; D001120:Arginine; D000242:Cyclic AMP; D006152:Cyclic GMP; D013936:Thymidine; D007213:Indomethacin