title: Inhibition of interleukin-1β-induced matrix metalloproteinase expression in human corneal fibroblasts by tranilast.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) mediate the degradation of extracellular matrix proteins and are implicated in the pathogenesis of corneal ulceration. Tranilast, a clinically approved antiallergy drug, has been found to exert various anti-inflammatory effects. We examined the effects of this agent on MMP expression in cultured corneal fibroblasts.
  
  
  METHODS
  Human corneal fibroblasts were cultured in the absence or presence of interleukin-1β (IL-1β) or tranilast. The release of MMPs into culture supernatants was assessed by immunoblot analysis and gelatin zymography, and the cellular abundance of MMP mRNAs was determined by reverse transcription and real-time polymerase chain reaction analysis. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-κB (NF-κB) inhibitor IκB-α was examined by immunoblot analysis.
  
  
  RESULTS
  The IL-1β-induced expression of MMP-1, -2, and -3 in corneal fibroblasts was inhibited by tranilast in a concentration- and time-dependent manner. It was also attenuated by synthetic inhibitors of MAPK or NF-κB signaling pathways. Tranilast inhibited the IL-1β-induced phosphorylation of the MAPKs extracellular signal-regulated kinase (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK) as well as the phosphorylation and degradation of IκB-α. Tranilast did not exhibit cytotoxicity for corneal fibroblasts.
  
  
  CONCLUSIONS
  Tranilast inhibits the IL-1β-induced production of MMP-1, -2, and -3 by human corneal fibroblasts, with this action likely being mediated through suppression of MAPK and NF-κB signaling pathways. Tranilast thus warrants further investigation as a potential treatment for corneal ulceration on the basis of its inhibition of MMP expression in corneal fibroblasts.
authors.affiliation: Department of Pathology, First Hospital of Jilin University , Jilin , PR China .
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D060527:Corneal Keratocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D062367:ortho-Aminobenzoates; D000072000:NF-KappaB Inhibitor alpha; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases; C012293:tranilast
keywords: Corneal fibroblast; inflammation; interleukin-1β; matrix metalloproteinase; tranilast