title: Modulation of collagen synthesis by tumor necrosis factor alpha in cultured vascular smooth muscle cells.
abstract: Collagen synthesis in vascular smooth muscle cells (SMCs) after exposure to tumor necrosis factor alpha (TNF-alpha) was investigated using a culture system. The synthesis of collagenase-digestible proteins (CDP) and noncollagenous proteins (NCP) was evaluated by the [3H]proline incorporation. It was shown that TNF-alpha markedly suppresses the incorporation of [3H]proline into both CDP and NCP in confluent cultures of SMCs but not in sparse cultures of the cells. Such a marked suppression by TNF-alpha was not observed in confluent bovine aortic endothelial cells and human fibroblastic IMR-90 cells. In confluent SMCs, the synthesis of CDP was more strongly inhibited by TNF-alpha than that of NCP. When the CDP synthesis was stimulated by transforming growth factor beta, TNF-alpha suppressed the stimulation in both confluent and sparse SMCs. Human SMCs synthesized types I, III, IV and V collagens; TNF-alpha markedly decreased the relative proportion of types IV and V. It was therefore suggested that TNF-alpha modulates the collagen synthesis by SMCs depending on their cell density and modifies the formation of atherosclerotic lesions.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hiraga
authors.forename: T
authors.initials: T
authors.lastname: Kaji
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.forename: F
authors.initials: F
authors.lastname: Zisaki
authors.forename: K
authors.initials: K
authors.lastname: Iwata
authors.forename: F
authors.initials: F
authors.lastname: Koizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Katsuda
authors.forename: I
authors.initials: I
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D011392:Proline