Noguchi K, Ruwanpura S M P M, Yan M, Yoshida N, Ishikawa I
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Oral Microbiol Immunol. 2005 Feb;20(1):56-9. doi: 10.1111/j.1399-302X.2004.00187.x.
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.
在本研究中,我们调查了前列腺素(PG)E2对白细胞介素(IL)-1α刺激的人牙周膜细胞中基质金属蛋白酶(MMP)-13产生的影响。IL-1α增强了MMP-13和PGE2的产生。非选择性环氧化酶抑制剂吲哚美辛和特异性环氧化酶-2(COX-2)抑制剂NS-398显著增强了IL-1α诱导的牙周膜细胞中MMP-13的产生,尽管这两种药物完全抑制了IL-1α诱导的PGE2产生。外源性PGE2以剂量依赖性方式降低了IL-1α诱导的MMP-13 mRNA和蛋白的产生。选择性EP1受体激动剂17-苯基-ω-三降PGE2模拟了PGE2对IL-1α诱导的MMP-13 mRNA和蛋白产生的抑制作用。基于这些数据,我们认为COX-2依赖性PGE2通过人牙周膜细胞中的EP1受体下调IL-1α诱导的MMP-13产生。PGE2可能参与牙周病变中细胞外基质成分破坏的调节。