title: Down-regulation of inflammatory mediator synthesis and infiltration of inflammatory cells by MMP-3 in experimentally induced rat pulpitis.
abstract: BACKGROUND
  Matrix metalloproteinase (MMP)-3 is a member of the MMP family that degrades the extracellular matrix. Application of MMP-3 to injured pulp tissue induces angiogenesis and wound healing, but its anti-inflammatory effects are still unclear. Here, we evaluated the anti-inflammatory functions of MMP-3 in vitro and in vivo.
  
  
  METHODS
  Nitric oxide and inflammatory mediator synthesis in macrophages activated by lipopolysaccharide (LPS) was measured in the presence or absence of MMP-3. The mouse Mmp3 (mMmp3) expression vector containing full length cDNA sequence of mMmp3 or cDNA sequence of mMmp3 missing the signal peptide and pro-peptide regions was transfected to RAW264, a mouse macrophage cell line, and NO synthesis and inflammatory mediator expression were evaluated. Pulpal inflammation was histologically and immunohistochemically evaluated in a rat model of incisor pulpitis induced by the application of LPS for 9 hours in the presence or absence of MMP-3.
  
  
  RESULTS
  NO and pro-inflammatory mediator synthesis promoted by LPS was significantly down-regulated by MMP-3 in vitro. The full length of mMmp3 down-regulated the LPS-induced NO synthesis and chemical mediator mRNA expression, however the mMmp3 missing the signal peptide failed to block the NO synthesis induced by LPS. The numbers of major histocompatibility complex class II+ and CD68+ cells, which infiltrated into the rat incisor pulp tissues in response to the topical application of LPS, were significantly decreased by the application of MMP-3 in vivo.
  
  
  CONCLUSIONS
  These results indicate that MMP-3 possesses anti-inflammatory functions, suggesting its potential utility as an anti-inflammatory agent for pulpal inflammation.
authors.affiliation: Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Koyo
authors.initials: K
authors.lastname: Takimoto
authors.affiliation: Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: kawashima.n.endo@tmd.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawashima
authors.affiliation: Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Koizumi
authors.affiliation: Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mioko
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Aichi, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Suda
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000187:drug effects; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000032:analysis; D053583:Interleukin-1beta / Q000187:drug effects; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000032:analysis; D011671:Pulpitis / Q000276:immunology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D000097382:CD68 Molecule
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D051546:Cyclooxygenase 2; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019278:Matrix Metalloproteinase 3; D009569:Nitric Oxide; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Cytokine(s); inflammation; matrix metalloproteinase-3; pulp biology; pulpitis