Enamel matrix derivative exhibits anti-inflammatory properties in monocytes.
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.
Sato
Sunao
S
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.
Kitagawa
Masae
M
Sakamoto
Kiyako
K
Iizuka
Shinji
S
Kudo
Yasusei
Y
Ogawa
Ikuko
I
Miyauchi
Mutsumi
M
Chu
Emily Y
EY
Foster
Brian L
BL
Somerman
Martha J
MJ
Takata
Takashi
T
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
D000893:Anti-Inflammatory Agents; D003746:Dental Enamel Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C109069:enamel matrix proteins; D015232:Dinoprostone