Kurihara Y, Endo H, Akahoshi T, Kondo H
Division of Rheumatology, Department of Internal Medicine, Kitasato University School of Medicine, Kitasato, Kanagawa, Japan.
Clin Exp Immunol. 2001 Feb;123(2):323-30. doi: 10.1046/j.1365-2249.2001.01442.x.
To evaluate the role of the prostaglandin E receptor (EP) subtypes in the development of inflammatory synovitis, we examined EP subtype mRNA distribution in the synovial tissue of rats with adjuvant arthritis and the effect of selective EP agonists on cytokine production by cultured rat synovial cells. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization to measure the level of EP subtype (EP1, EP2, EP3, and EP4) mRNA expression in synovial tissues and cultured synovial cells from the arthritic joints of rats. RT-PCR and ELISA were used to analyse the effects of two selective EP agonists on IL-6 production by cultured rat synovial cells. EP2 and EP4 mRNA expression in inflamed synovial tissues was up-regulated. EP2 and EP4 mRNA were co-expressed in synovial macrophages and fibroblasts in inflamed tissues. EP4 and EP2 agonists both inhibited IL-1-induced IL-6 production. Our results suggest that prostaglandin E2 regulates the functions of synovial macrophages and fibroblasts through EP2 and EP4, which are induced by inflammatory stimuli in rats with adjuvant arthritis.
为评估前列腺素E受体(EP)亚型在炎性滑膜炎发展中的作用,我们检测了佐剂性关节炎大鼠滑膜组织中EP亚型mRNA的分布,以及选择性EP激动剂对培养的大鼠滑膜细胞细胞因子产生的影响。我们使用逆转录聚合酶链反应(RT-PCR)和原位杂交技术来测定大鼠关节炎关节滑膜组织和培养的滑膜细胞中EP亚型(EP1、EP2、EP3和EP4)mRNA的表达水平。采用RT-PCR和酶联免疫吸附测定(ELISA)分析两种选择性EP激动剂对培养的大鼠滑膜细胞产生白细胞介素-6(IL-6)的影响。炎性滑膜组织中EP2和EP4 mRNA的表达上调。EP2和EP4 mRNA在炎性组织的滑膜巨噬细胞和成纤维细胞中共同表达。EP4和EP2激动剂均抑制白细胞介素-1诱导的IL-6产生。我们的结果表明,前列腺素E2通过EP2和EP4调节滑膜巨噬细胞和成纤维细胞的功能,EP2和EP4在佐剂性关节炎大鼠中由炎性刺激诱导产生。