Noguchi K, Iwasaki K, Ishikawa I
Department of Periodontology, Faculty of Dentistry, Tokyo Medical & Dental University, Japan.
J Periodontal Res. 1999 Jul;34(5):277-81. doi: 10.1111/j.1600-0765.1999.tb02254.x.
Prostaglandin F2 alpha (PGF2 alpha) is a bioactive lipid mediator, which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2 alpha in the disease are not well understood. In the present study, we investigated the effect of PGF2 alpha on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) and the effect of PGF2 alpha on ICAM-1 expression elicited by proinflammatory cytokines, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha) in the cells. PGF2 alpha-stimulated HGF expressed ICAM-1 expression in a time- and dose-dependent manner. IFN-gamma-elicited ICAM-1 expression was synergistically increased by PGF2 alpha, whereas TNF alpha-induced ICAM-1 expression was slightly inhibited by PGF2 alpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF2 alpha-induced effect on ICAM-1 expression. Furthermore, signal transduction for the regulation of ICAM-1 by PGF2 alpha was investigated using N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), a calcium calmodulin antagonist, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C (PKC). W-7 and H-7, remarkably, suppressed PGF2 alpha-induced ICAM-1 expression and synergistic increase of ICAM-1 expression by combination of PGF2 alpha and IFN-gamma, while IFN-gamma-elicited ICAM-1 expression was only partially inhibited by W-7 and H-7. From these data, we suggest that PGF2 alpha upregulates ICAM-1 expression in HGF and synergistically enhances IFN-gamma-induced ICAM-1 expression through FP receptor by calcium calmodulin-dependent and PKC-dependent pathways. PGF2 alpha may be involved in the pathology of periodontal disease by upregulating ICAM-1 expression in HGF.
前列腺素F2α（PGF2α）是一种生物活性脂质介质，有人认为它参与了牙周病的发病机制。然而，PGF2α在该疾病中的作用尚未完全明确。在本研究中，我们调查了PGF2α对人牙龈成纤维细胞（HGF）中细胞间黏附分子-1（ICAM-1）表达的影响，以及PGF2α对促炎细胞因子干扰素-γ（IFN-γ）和肿瘤坏死因子α（TNFα）诱导的细胞中ICAM-1表达的影响。PGF2α刺激的HGF以时间和剂量依赖的方式表达ICAM-1。PGF2α协同增加了IFN-γ诱导的ICAM-1表达，而PGF2α对TNFα诱导的ICAM-1表达有轻微抑制作用。氟前列烯醇，一种选择性FP受体激动剂，可模拟PGF2α对ICAM-1表达的诱导作用。此外，使用钙调蛋白拮抗剂N-（6-氨基己基）-5-氯-1-萘磺酰胺（W-7）和蛋白激酶C（PKC）抑制剂1-（5-异喹啉磺酰基）-2-甲基哌嗪（H-7）研究了PGF2α调节ICAM-1的信号转导。值得注意的是，W-7和H-7抑制了PGF2α诱导的ICAM-1表达以及PGF2α与IFN-γ联合诱导的ICAM-1表达的协同增加，而W-7和H-7仅部分抑制了IFN-γ诱导的ICAM-1表达。根据这些数据，我们认为PGF2α上调HGF中ICAM-1的表达，并通过钙调蛋白依赖性和PKC依赖性途径通过FP受体协同增强IFN-γ诱导的ICAM-1表达。PGF2α可能通过上调HGF中ICAM-1的表达参与牙周病的病理过程。
