Tranilast restores cytokine-induced nitric oxide production against platelet-derived growth factor in vascular smooth muscle cells.
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.
Hishikawa
K
K
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nakaki
T
T
Hirahashi
J
J
Marumo
T
T
Saruta
T
T
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*
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