title: Enamel matrix derivative exhibits anti-inflammatory properties in monocytes.
abstract: BACKGROUND
  Enamel matrix derivative (EMD) is used clinically to promote periodontal tissue regeneration with variable efficacy. EMD application results in significantly higher frequencies of sites without clinical signs of inflammation; additionally, patients receiving EMD therapy report significantly less post-treatment discomfort. However, there are few reports that focus on defining the biologic mechanisms for the observed anti-inflammatory effects of EMD. The aim of this study was to evaluate the influence of EMD on inflammatory-associated markers using an in vitro monocyte assay.
  
  
  METHODS
  Rat monocytes were exposed to lipopolysaccharide (LPS; 100 ng/ml from Escherichia coli or Actinobacillus actinomycetemcomitans) along with EMD (0, 50, 100, or 200 microg/ml). Levels of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) in conditioned media were analyzed by enzyme-linked immunosorbent assay. In addition, the effects of exogenous PGE(2) on TNF-alpha production from LPS-stimulated monocytes were determined.
  
  
  RESULTS
  LPS-stimulated monocytes exposed to EMD exhibited a decrease in TNF-alpha production (0.10- to 0.52-fold) and an increase in PGE(2) production (1.31- to 2.71-fold) compared to controls not treated with EMD. Exogenously applied PGE(2) decreased TNF-alpha production by LPS-stimulated monocytes in a dose-dependent manner, and EMD treatment enhanced this PGE(2)-mediated inhibition of TNF-alpha production.
  
  
  CONCLUSIONS
  In addition to EMD's published role in inducing proliferation, migration, adhesion, mineralization, and differentiation of periodontal ligament cells, our results indicated that EMD modulates two inflammation-associated factors, TNF-alpha and PGE(2), in monocytes.
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Sato
authors.forename: Masae
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Kiyako
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Iizuka
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogawa
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Miyauchi
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chu
authors.forename: Brian L
authors.initials: BL
authors.lastname: Foster
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Somerman
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D015232:Dinoprostone / Q000819:agonists* / Q000096:biosynthesis / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D003746:Dental Enamel Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C109069:enamel matrix proteins; D015232:Dinoprostone