title: Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1{beta}-activated human endothelial cells.
abstract: The aim of this study was to determine the effect of ethanol (EtOH) on endothelial monocyte chemotactic protein-1 (MCP-1) expression. IL-1beta increased the production of MCP-1 by human umbilical vein endothelial cells from undetectable levels to approximately 900 pg/ml at 24 h. EtOH dose-dependently inhibited IL-1beta-stimulated MCP-1 secretion as determined by ELISA: 25 +/- 1%, 35 +/- 7%, and 65 +/- 5% inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with inhibition of monocyte adhesion to activated endothelial cells. Similarly, EtOH dose-dependently inhibited IL-1beta-stimulated MCP-1 mRNA expression. Experiments with actinomycin D demonstrated that EtOH decreased the stability of MCP-1 mRNA. In addition, EtOH significantly reduced NF-kappaB and AP-1 binding activity induced by IL-1beta and inhibited MCP-1 gene transcription. Binding of (125)I-labeled MCP-1 to its receptor (CCR2) on THP-1 human monocytic cells was not affected by EtOH treatment. Modulation of the expression of MCP-1 represents a mechanism whereby EtOH could inhibit atherogenesis by blocking the crucial early step of monocyte adhesion and subsequent recruitment to the subendothelial space. These actions of EtOH may underlie, in part, its cardiovascular protective effects in vivo.
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Cullen
authors.forename: Shariq
authors.initials: S
authors.lastname: Sayeed
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Theodorakis
authors.forename: James V
authors.initials: JV
authors.lastname: Sitzmann
authors.forename: Paul A
authors.initials: PA
authors.lastname: Cahill
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Redmond
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology
chemical_list: C111835:CCL2 protein, human; D002492:Central Nervous System Depressants; D018932:Chemokine CCL2; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D000431:Ethanol