Noguchi K, Iwasaki K, Shitashige M, Endo H, Kondo H, Ishikawa I
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Japan.
J Dent Res. 2000 Dec;79(12):1955-61. doi: 10.1177/00220345000790120601.
Prostaglandin E2 (PGE2), which exerts its actions via EP receptors (EP1, EP2, EP3, and EP4), is a bioactive metabolite of arachidonic acid produced by cyclooxygenase (COX)-1 and/or COX-2. We have previously demonstrated that PGE2 down-regulates intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1beta (IL-1beta)-stimulated human gingival fibroblasts (HGF). In the present study, we investigated which COX was involved in down-regulation of ICAM-1 expression by PGE2 in IL-1beta-stimulated HGF and which subtypes of EP receptors modulated the ICAM-1 expression. NS-398, a specific COX-2 inhibitor, completely inhibited PGE2 production by IL-1beta-stimulated HGF, as did indomethacin, a COX-1/COX-2 inhibitor. Northern blot analysis and immunocytochemical staining showed that mRNA and protein of COX-2 were expressed in IL-1beta-challenged HGF, but not in unstimulated HGF, and that the expression of mRNA and protein of COX-1 was similar both in unstimulated and in stimulated cells. NS-398 and indomethacin enhanced ICAM-1 expression in IL-1beta-challenged HGF. EP1, EP2, and EP4 receptor mRNA was expressed in HGF according to reverse-transcription/polymerase chain-reaction. PGE2, 11-deoxy-PGE1 (a selective EP2/EP4 agonist), and Butaprost (a selective EP2 agonist) attenuated IL-1beta-elicited ICAM-1 expression, although Butaprost was less potent than PGE2 and 11-deoxy-PGE1. AH-23848B, an EP4 antagonist, antagonized the inhibitory effect of IL-1beta-elicited ICAM-1 expression by PGE2. Sulprostone, an EP1/EP3 agonist, had no effect on IL-1beta-elicited ICAM-1 expression. Analysis of these data suggests that COX-2-derived PGE2 down-regulates ICAM-1 expression via EP2/EP4 receptors in IL-1beta-stimulated HGF.
前列腺素E2（PGE2）是一种由环氧化酶（COX）-1和/或COX-2产生的花生四烯酸生物活性代谢产物，它通过EP受体（EP1、EP2、EP3和EP4）发挥作用。我们之前已经证明，PGE2可下调白细胞介素-1β（IL-1β）刺激的人牙龈成纤维细胞（HGF）中细胞间黏附分子-1（ICAM-1）的表达。在本研究中，我们调查了在IL-1β刺激的HGF中，哪种COX参与了PGE2对ICAM-1表达的下调，以及EP受体的哪些亚型调节了ICAM-1的表达。NS-398是一种特异性COX-2抑制剂，它与COX-1/COX-2抑制剂吲哚美辛一样，完全抑制了IL-1β刺激的HGF产生PGE2。Northern印迹分析和免疫细胞化学染色显示，COX-2的mRNA和蛋白在IL-1β刺激的HGF中表达，但在未刺激的HGF中不表达，并且COX-1的mRNA和蛋白在未刺激和刺激细胞中的表达相似。NS-398和吲哚美辛增强了IL-1β刺激的HGF中ICAM-1的表达。根据逆转录/聚合酶链反应，EP1、EP2和EP4受体mRNA在HGF中表达。PGE2、11-脱氧-PGE1（一种选择性EP2/EP4激动剂）和布他前列素（一种选择性EP2激动剂）减弱了IL-1β诱导的ICAM-1表达，尽管布他前列素的效力低于PGE2和11-脱氧-PGE1。EP4拮抗剂AH-23848B拮抗了PGE2对IL-1β诱导的ICAM-1表达的抑制作用。EP1/EP3激动剂舒前列素对IL-1β诱导的ICAM-1表达没有影响。对这些数据的分析表明，COX-2衍生的PGE2通过EP2/EP4受体下调IL-1β刺激的HGF中ICAM-1的表达。
