Prostaglandin E2 (PGE2) downregulates interleukin (IL)-1alpha-induced IL-6 production via EP2/EP4 subtypes of PGE2 receptors in human periodontal ligament cells.

OBJECTIVES: Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors, which are divided into four subtypes, EP1, EP2, EP3 and EP4. In the present study, we examined whether PGE2 regulated interleukin (IL)-1alpha-induced IL-6 production in human periodontal ligament (PDL) cells and if so, which subtypes of PGE2 receptors were involved. METHODS: PDL cells were stimulated with vehicle or IL-1alpha in the presence or absence of indomethacin (a cylooxygenase inhibitor), PGE2 or various EP agonists. IL-6 and PGE2 levels were measured by enzyme-linked immunosorbent assay. EP receptor mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Indomethacin significantly enhanced IL-1alpha-induced IL-6 production by PDL cells, although it completely inhibited IL-1alpha-induced PGE2 production. Exogenous PGE2 significantly suppressed IL-1alpha-induced IL-6 production. Butaprost, a selective EP2 agonist, and ONO-AE1-329, a selective EP4 agonist, significantly inhibited IL-1alpha-induced IL-6 production, although 17-phenyl-omega-trinor PGE2, an EP1 agonist, and ONO-AP-324, an EP3 agonist, did not affect it. RT-PCR analysis showed that EP2 and EP4 mRNA was expressed in PDL cells. CONCLUSIONS: We suggest that PGE2 downregulates IL-1alpha-induced IL-6 production via EP2/EP4 receptors in human PDL cells.

Er:YAG laser irradiation increases prostaglandin E production via the induction of cyclooxygenase-2 mRNA in human gingival fibroblasts.

BACKGROUND AND OBJECTIVES: It has been reported that both prostaglandin E2 (PGE2) and Er:YAG laser irradiation accelerate wound healing. The stimulatory action of laser seems to occur during the proliferative stage of healing by stimulation of prostaglandin E2 and cyclooxygenase-2 (COX-2), which are crucial early mediators in the natural healing process. We have then investigated the effect of Er:YAG laser irradiation on PGE2 production and COX-2 gene expression in human gingival fibroblast in vitro. MATERIAL AND METHODS: Cultured fibroblasts were exposed to low-power Er:YAG laser irradiation with an energy density of 3.37 J/cm2. The amount of PGE2 production was measured by enzyme-linked immunosorbent assay (ELISA). COX-2 mRNA level, which is a critical enzyme for PGE2 production, was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Er:YAG laser significantly increased PGE2 production by human gingival fibroblasts. COX-2 mRNA, which was hardly detectable in control, increased dramatically after irradiation. COX-2 inhibitor, NS398, completely inhibited the PGE2 synthesis stimulated by Er:YAG laser irradiation. CONCLUSION: Our results showed that Er:YAG laser irradiation appears to exert its stimulative action on gingival fibroblasts proliferation through the production of PGE2 via the expression of COX-2. This should be considered as one of the important regulatory pathways to accelerate wound healing after Er:YAG laser irradiation.

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.

Prostaglandin E2 regulates interleukin-1beta-induced matrix metalloproteinase-3 production in human gingival fibroblasts.

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)-1beta-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-1beta-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-1beta-induced MMP-3 production, and 17-phenyl-omega-trinor PGE2 (an EP1 agonist) mimicked the PGE(2) effect in HGF from healthy and periodontally diseased tissues, respectively. Analysis of these data suggests that, in HGF from healthy tissue, IL-1beta-induced MMP-3 production is down-regulated by PGE2 via EP2 and EP4 receptors, whereas in cells from periodontally diseased tissue, IL-1beta-induced MMP-3 production is up-regulated via EP1 receptors. Different regulation of IL-1beta-induced MMP-3 production by PGE2 between healthy and periodontally diseased tissues may be involved in the pathogenesis of periodontal disease.