Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02027 (Tranilast)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.
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PMID:Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages. 128 75

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.
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PMID:Tranilast restores cytokine-induced nitric oxide production against platelet-derived growth factor in vascular smooth muscle cells. 885 74