Prostaglandin E2Regulates 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 PGE2regulated 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, PGE2down-regulated IL-1β-induced MMP-3 production, whereas in HGF from periodontitis patients, PGE2enhanced it. Butaprost (an EP2agonist) and ONO-AE1-329 (an EP4agonist) suppressed IL-1β-induced MMP-3 production, and 17-phenyl-ω-trinor PGE2(an EP1agonist) mimicked the PGE2effect 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 PGE2via EP2and EP4receptors, whereas in cells from periodontally diseased tissue, IL-1β-induced MMP-3 production is up-regulated via EP1receptors. Different regulation of IL-1β-induced MMP-3 production by PGE2between healthy and periodontally diseased tissues may be involved in the pathogenesis of periodontal disease.