PMID- 9405974 OWN - NLM STAT- MEDLINE DCOM- 19980115 LR - 20181201 IS - 0018-5043 (Print) IS - 0018-5043 (Linking) VI - 29 IP - 10 DP - 1997 Oct TI - Cilostazol, a cAMP phosphodiesterase inhibitor, attenuates the production of monocyte chemoattractant protein-1 in response to tumor necrosis factor-alpha in vascular endothelial cells. PG - 491-5 AB - The induction of monocyte chemoattractant protein-1 (MCP-1) in vascular endothelial cells is thought to be an initial event in the development of atherosclerotic lesions. Therefore, inhibition of MCP-1 production may exhibit some effects in preventing atherosclerosis. In the present study, we found that 10 microM cilostazol, a cAMP phosphodiesterase inhibitor, increased the intracellular cAMP content by a twenty-five times of the basal level and resulted in the reduction of basal MCP-1 release by 41% from 168 +/- 11 ng/24 hr/mg protein to 99 +/- 14 ng/24 hr/mg protein (P < 0.001) from cultured human umbilical vein endothelial cells. Furthermore, 10 microM cilostazol also significantly attenuated the dose-dependent increment of MCP-1 production by tumor necrosis factor-alpha. The inhibition was consistent with the reduction of MCP-1 mRNA level, possibly through reduced activation of transcription factor NF-kappa B level. Similarly, 1 mM dibutyryl cAMP inhibited MCP-1 production in endothelial cells. These data suggest that cilostazol inhibits MCP-1 production through increased intracellular cAMP levels and modulation of its expression in vascular endothelial cells. FAU - Nishio, Y AU - Nishio Y AD - Third Department of Medicine, Shiga University of Medical Science, Japan. FAU - Kashiwagi, A AU - Kashiwagi A FAU - Takahara, N AU - Takahara N FAU - Hidaka, H AU - Hidaka H FAU - Kikkawa, R AU - Kikkawa R LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (Phosphodiesterase Inhibitors) RN - 0 (Platelet Aggregation Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Tetrazoles) RN - 0 (Tumor Necrosis Factor-alpha) RN - 63X7MBT2LQ (Bucladesine) RN - E0399OZS9N (Cyclic AMP) RN - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases) RN - N7Z035406B (Cilostazol) SB - IM MH - 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors MH - Bucladesine/pharmacology MH - Cells, Cultured MH - Chemokine CCL2/*antagonists & inhibitors/genetics MH - Cilostazol MH - Cyclic AMP/*biosynthesis MH - Endothelium, Vascular/cytology/*drug effects/metabolism MH - Humans MH - NF-kappa B/antagonists & inhibitors MH - Phosphodiesterase Inhibitors/*pharmacology MH - Platelet Aggregation Inhibitors/pharmacology MH - RNA, Messenger/antagonists & inhibitors MH - Tetrazoles/*pharmacology MH - Tumor Necrosis Factor-alpha/*metabolism/pharmacology MH - Umbilical Veins/cytology/drug effects/metabolism EDAT- 1997/12/24 00:00 MHDA- 1997/12/24 00:01 CRDT- 1997/12/24 00:00 PHST- 1997/12/24 00:00 [pubmed] PHST- 1997/12/24 00:01 [medline] PHST- 1997/12/24 00:00 [entrez] AID - 10.1055/s-2007-979086 [doi] PST - ppublish SO - Horm Metab Res. 1997 Oct;29(10):491-5. doi: 10.1055/s-2007-979086.