Prostaglandin E 2 Regulates Interleukin-1β-induced Matrix Metalloproteinase-3 Production in Human Gingival Fibroblasts

Abstract

Prostaglandin E₂ (PGE₂) exerts its biological actions via EP receptors (EP₁, EP₂, EP₃, and EP₄). In the present study, we investigated whether PGE₂ regulated interleukin (IL)-1β-induced matrix metalloproteinase (MMP)-3 production in human gingival fibroblasts (HGF) derived from periodontally healthy subjects and diseased patients. In HGF from healthy gingiva, PGE₂ down-regulated IL-1β-induced MMP-3 production, whereas in HGF from periodontitis patients, PGE₂ enhanced it. Butaprost (an EP₂ agonist) and ONO-AE1-329 (an EP₄ agonist) suppressed IL-1β-induced MMP-3 production, and 17-phenyl-ω-trinor PGE₂ (an EP₁ agonist) mimicked the PGE₂ effect in HGF from healthy and periodontally diseased tissues, respectively. Analysis of these data suggests that, in HGF from healthy tissue, IL-1β-induced MMP-3 production is down-regulated by PGE₂ via EP₂ and EP₄ receptors, whereas in cells from periodontally diseased tissue, IL-1β-induced MMP-3 production is up-regulated via EP₁ receptors. Different regulation of IL-1β-induced MMP-3 production by PGE₂ between healthy and periodontally diseased tissues may be involved in the pathogenesis of periodontal disease.

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