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)

1. First developed as an antiallergic drug, tranilast inhibits chemical mediator release from mast cells. In the present study, we examine the effects of tranilast on angiogenesis in vitro and in vivo and discuss the application of tranilast for angiogenic diseases. 2. Tranilast inhibited significantly the proliferation (IC50: 136 microM, 95% confidence limits: 134-137 microM) and vascular endothelium growth factor (VEGF)-induced chemotaxis (IC50: 135 microM, 95% confidence limits: 124-147 microM) of human dermal microvascular endothelial cells (HDMECs) at concentrations greater than 25 micrograms ml-1. No toxicity to HDMECs measuring by LDH release and no inhibitory effects on metalloproteinase (MMP)-2 and MMP-9 activity were observed even at 100 micrograms ml-1 (306 microM). 3. Tube formation of HDMECs cultured on the matrigel as an in vitro angiogenesis model was inhibited by tranilast in a concentration-dependent manner. The IC50 value and 95% confidence limits were 175 microM and 151-204 microM, respectively. 4. In vivo angiogenesis was induced in mice by the subcutaneous injection of matrigel containing 30 ng ml-1 VEGF and 64 micrograms ml-1 heparin. Tranilast was administered orally twice a day for 3 days. Tranilast dose-dependently suppressed angiogenesis in the matrigel and a significant change was observed at a dose of 300 mg kg-1. 5. These results indicate that tranilast is an angiogenesis inhibitor which may be beneficial for the improvement of angiogenic diseases such as proliferative diabetic retinopathy, age-related macular degeneration, tumour invasion and rheumatoid arthritis.
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PMID:Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo. 940 70

Tranilast is an anti-allergic agent that blocks the release of chemical mediators, such as histamine and leukotrienes from mast cells, and has been reported to suppress keloid and hypertrophic scar formation. Since matrix metalloproteinases (MMPs) play an essential role in tissue remodelling, this study was undertaken to determine whether tranilast suppresses MMP production from neutrophils after lipopolysaccharide (LPS) stimulation in-vitro. Neutrophils from five healthy donors (1 x 10(5) cells/mL) were stimulated with 1.0 microg mL(-1) LPS in the presence or absence of various concentrations of tranilast for 24 h. MMP-7, MMP-8, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels in the culture supernatants were assayed by ELISA. In addition, the influence of tranilast on MMP mRNA expression and transcriptional factor activation in cells cultured for 12 h and 4 h was also evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Tranilast inhibited MMP and TIMP-1 production from neutrophils when cells were treated with the agent at more than 5.0 x 10(-5) M. It also suppressed MMP mRNA expression and transcriptional factor activation induced in neutrophils by LPS stimulation. The results suggest that tranilast inhibits the formation of keloid scarring through the suppression of factors such as MMPs and TIMP, which are essential for tissue remodelling, from inflammatory cells.
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PMID:Effect of tranilast on matrix metalloproteinase production from neutrophils in-vitro. 1639 68