Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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

The effect of Tranilast [N-(3,4-dimethoxycinnamoyl) anthranilic acid] on the synthesis of prostaglandin D2 (PGD2) by homogenates of rat peritoneal mast cells was investigated. The major cyclooxygenase product formed by mast cell homogenates was PGD2, smaller quantities of PGE2 and PGF2 alpha were also formed. Tranilast suppressed the production of PGD2 in a dose-dependent manner with an IC50 of 0.1 mM. This suppression was due to inhibition of PGD synthetase, but not cyclooxygenase, since the formation of PGE2 and PGF2 alpha were unchanged at a 0.1 mM concentration. In addition, the glutathione-dependent conversion of [14C]PGH2 to PGD2 by PGD synthetase (PGH-D isomerase, EC 5.3.99.2) was inhibited by Tranilast, with 50% inhibition achieved at 0.08 mM in broken cell preparations of rat peritoneal mast cells. Tranilast also inhibited purified rat spleen and brain PGD synthetases. Furthermore, Tranilast prevented the PGD2 generation from intact mast cells stimulated by the calcium ionophore A23187. These results suggest that Tranilast exerts some of its therapeutic effects by prevention of PGD2 generation in mast cells and some other tissues.
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PMID:Inhibitory effect of tranilast on prostaglandin D synthetase. 247 13