Down-regulation of interleukin-1alpha-induced matrix metalloproteinase-13 expression via EP1 receptors by prostaglandin E2 in human periodontal ligament cells.
In the present study, we investigated the effect of prostaglandin (PG) E2 on matrix metalloproteinase (MMP)-13 production in human periodontal ligament cells stimulated with interleukin (IL)-1alpha. IL-1alpha enhanced both MMP-13 and PGE2 production. Indomethacin, a nonselective cyclooxygenase inhibitor, and NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly enhanced IL-1alpha-induced MMP-13 production in periodontal ligament cells, although both the agents completely inhibited IL-1alpha-induced PGE2 production. Exogenous PGE2 reduced IL-1alpha-induced MMP-13 mRNA and protein production in a dose-dependent manner. 17-phenyl-omega-trinor PGE2, a selective EP1 receptor agonist, mimicked the inhibitory effect of PGE2 on IL-1alpha-induced MMP-13 mRNA and protein production. On the basis of these data, we suggest that COX-2-dependent PGE2 down-regulates IL-1alpha-elicited MMP-13 production via EP1 receptors in human periodontal ligament cells. PGE2 may be involved in the regulation of destruction of extracellular matrix components in periodontal lesions.
Noguchi
K
K
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. kazuyuki-noguchi.peri@tmd.ac.jp
Ruwanpura
S M P M
SM
Yan
M
M
Yoshida
N
N
Ishikawa
I
I
D017364:Collagenases / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13; D009578:Nitrobenzenes / Q000494:pharmacology; D010513:Periodontal Ligament / Q000187:drug effects* / Q000378:metabolism; D018078:Receptors, Prostaglandin E; D013449:Sulfonamides / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D009578:Nitrobenzenes; D018078:Receptors, Prostaglandin E; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D015232:Dinoprostone; D007213:Indomethacin