Noguchi Kazuyuki, Miyauchi Mutsumi, Oka Hiroko, Komaki Motohiro, Somerman Martha J, Takata Takashi
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
J Periodontol. 2007 Jan;78(1):135-40. doi: 10.1902/jop.2007.060257.
Prostaglandin E(2) (PGE(2)), which exerts its biologic actions via EP receptors (EP(1), EP(2), EP(3,) and EP(4)), is a bioactive metabolite of arachidonic acid that is produced by cyclooxygenase (COX)-1 and/or COX-2. In the present study, we investigated whether a mouse cementoblast cell line, OCCM-30 cells, that was stimulated with interleukin (IL)-1alpha produced COX-2-dependent PGE(2) and whether the produced PGE(2) affected IL-1alpha-induced IL-6 production.
OCCM-30 cells were stimulated with vehicle or IL-1alpha in the presence or absence of indomethacin (a COX-1/COX-2 inhibitor), NS-398 (a specific COX-2 inhibitor), PGE(2), and EP receptor agonists. PGE(2) and IL-6 levels were assayed by enzyme linked immunosorbent assay.
IL-1alpha induced PGE(2) production in a time-dependent fashion. Indomethacin and NS-398 completely inhibited IL-1alpha-induced PGE(2) production. 17-phenyl-omega-trinor PGE(2) (an EP(1) agonist) and an EP(4) agonist mimicked PGE(2) enhancement of IL-1alpha-induced IL-6 production in OCCM-30 cells.
From these data, we suggest that IL-1alpha induced PGE(2) production in a COX-2-dependent manner in OCCM-30 cells and that the COX-2-derived PGE(2) upregulates IL-1alpha-elicited IL-6 production via EP(1) and/or EP(4) receptors. PGE(2) and IL-6 produced by cementoblasts may be involved in the pathogenesis of periodontal disease.
前列腺素E2（PGE2）是花生四烯酸的一种生物活性代谢产物，由环氧化酶（COX）-1和/或COX-2产生，它通过EP受体（EP1、EP2、EP3和EP4）发挥其生物学作用。在本研究中，我们调查了白细胞介素（IL）-1α刺激的小鼠成牙骨质细胞系OCCM-30细胞是否产生COX-2依赖性PGE2，以及所产生的PGE2是否影响IL-1α诱导的IL-6产生。
在存在或不存在吲哚美辛（一种COX-1/COX-2抑制剂）、NS-398（一种特异性COX-2抑制剂）、PGE2和EP受体激动剂的情况下，用载体或IL-1α刺激OCCM-30细胞。通过酶联免疫吸附测定法检测PGE2和IL-6水平。
IL-1α以时间依赖性方式诱导PGE2产生。吲哚美辛和NS-398完全抑制IL-1α诱导的PGE2产生。17-苯基-ω-三降PGE2（一种EP1激动剂）和一种EP4激动剂模拟了PGE2增强OCCM-30细胞中IL-1α诱导的IL-6产生。
根据这些数据，我们认为IL-1α在OCCM-30细胞中以COX-2依赖性方式诱导PGE2产生，并且COX-2衍生的PGE2通过EP1和/或EP4受体上调IL-1α诱导的IL-6产生。成牙骨质细胞产生的PGE2和IL-6可能参与牙周疾病的发病机制。
