title: Targeting TNF-α suppresses the production of MMP-9 in human salivary gland cells.
abstract: OBJECTIVE
  Tumour necrosis factor-α (TNF-α) is a pleiotropic cytokine that plays an essential role in inflammation and apoptosis. Our previous study suggested that TNF-α-induced activation of matrix metalloproteinase-9 (MMP-9) resulted in the destruction of acinar tissue in the salivary glands of patients with Sjögren's syndrome (SS) via disruption of the acinar cell-basement membrane. Recently, a wide array of biological agents has been designed to inhibit TNF, including etanercept and adalimumab. In this study, we demonstrate the suppressive effect of anti-TNF agents on TNF-α-induced MMP-9 production in NS-AV-AC, an immortalized human salivary gland acinar cell line.
  
  
  METHODS
  NS-AV-AC cells were treated with etanercept or adalimumab after TNF-α treatment. MMP-9 production and enzymatic activity were, respectively, visualized by real-time PCR and ELISA assay, and evaluated by gelatin zymography, and apoptosis was evaluated by DNA fragmentation assay.
  
  
  RESULTS
  TNF-α induced the production of MMP-9 in NS-SV-AC cells. However, this production was greatly inhibited by treatment with etanercept or adalimumab. In addition, TNF-α-induced DNA fragmentation was prevented by treatment with etanercept or adalimumab.
  
  
  CONCLUSIONS
  These results may indicate that anti-TNF agents would have therapeutic efficacy for preventing destruction of the acinar structure in the salivary glands of patients with SS.
authors.affiliation: Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima, Graduate Faculty of Dentistry, Tokushima 770-8504, Japan. Electronic address: aota.keiko@tokushima-u.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Aota
authors.forename: Masayuki
authors.initials: M
authors.lastname: Azuma
mesh_terms: D061354:Acinar Cells / Q000378:metabolism*; D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D000068879:Adalimumab; D000068800:Etanercept
keywords: Matrix metalloproteinase-9; Salivary gland cells; Tumour necrosis factor-α