title: Inhibition of gap junctional intercellular communication between primary human smooth muscle cells by tumor necrosis factor alpha.
abstract: Tumor necrosis factor alpha (TNF alpha), a pleiotrophic cytokine present in atherosclerotic lesions, caused a dose-dependent and persistent reduction in gap junctional intercellular communication (GJIC) between primary human smooth muscle cells in vitro. A continuous presence of TNF alpha was required for this persistent inhibition. Pretreatment of smooth muscle cells with ascorbic acid, alpha-tocopherol or glutathione prevented this inhibition of GJIC by TNF alpha. The persistent blockage of GJIC by continuous exposure to TNF alpha suggests that TNF alpha may share some mechanistic similarities with exogenous tumor promoters. Furthermore, this reduction in GJIC by TNF alpha may provide an additional link between the processes of atherosclerosis and carcinogenesis. The protection afforded by antioxidant compounds suggests a role for active oxygen species in the promotion stage of atherosclerosis.
authors.affiliation: Department of Toxicology, Agricultural University Wageningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Mensink
authors.forename: L H
authors.initials: LH
authors.lastname: de Haan
authors.forename: C M
authors.initials: CM
authors.lastname: Lakemond
authors.forename: C A
authors.initials: CA
authors.lastname: Koelman
authors.forename: J H
authors.initials: JH
authors.lastname: Koeman
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000209:etiology; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D003603:Cytotoxins / Q000037:antagonists & inhibitors / Q000502:physiology / Q000633:toxicity*; D004347:Drug Interactions; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000633:toxicity; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D003603:Cytotoxins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha