Effect of tranilast on matrix metalloproteinase production from neutrophils in-vitro.
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.
Shimizu
Toshiyuki
T
Department of Otorhinolaryngology, School of Medicine, Showa University, Tokyo, Japan.
Kanai
Ken-Ichi
K
Kyo
Yoshiyuki
Y
Asano
Kazuhito
K
Hisamitsu
Tadashi
T
Suzaki
Harumi
H
D000328:Adult; D018926:Anti-Allergic Agents / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D062367:ortho-Aminobenzoates; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; C012293:tranilast