title: Tranilast restores cytokine-induced nitric oxide production against platelet-derived growth factor in vascular smooth muscle cells.
abstract: Tranilast has been reported to reduce restenosis rate after angioplasty, but its mechanism is still unclear. We investigated the effect of tranilast against platelet-derived growth factor (PDGF) in PDGF's proliferative effect and PDGF's inhibitory effect on cytokine-induced nitric oxide (NO) production in vascular smooth muscle cells (VSMC). NO production was measured by Griess reaction. NO synthase (NOS) protein was evaluated by Western blot with monoclonal anti-rat inducible NOS antibody. A combination of interleukin-1 beta (IL-1 beta 1 ng/ml), tumor necrosis factor-alpha (TNF-alpha 2,000 U/ml), and lipopolysaccharide (100 ng/ml) significantly increased NO production and NOS protein, and tranilast significantly enhanced both in a dose-dependent manner. PDGF (100 ng/ml) significantly reduced both cytokine-induced NO production and NOS protein induction, but tranilast completely abolished these inhibitory effects. In the presence of cytokines, serum-stimulated cell proliferation was significantly inhibited by cytokine-induced NO, whereas PDGF-stimulated proliferation was not. On the other hand, tranilast not only inhibited the proliferative effect of PDGF directly, but also restored cytokine-induced NO production and its antiproliferative effect in the presence of PDGF.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hishikawa
authors.forename: T
authors.initials: T
authors.lastname: Nakaki
authors.forename: J
authors.initials: J
authors.lastname: Hirahashi
authors.forename: T
authors.initials: T
authors.lastname: Marumo
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D062367:ortho-Aminobenzoates; D009569:Nitric Oxide; D004247:DNA; D019001:Nitric Oxide Synthase; C012293:tranilast