Luo Cheng, Kallajoki Markku, Gross Rene, Mulari Mika, Teros Tamara, Ylinen Laura, Mäkinen Marjaana, Laine Jukka, Simell Olli
Juvenile Diabetes Research Foundation (FDRF) Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland.
Cell Tissue Res. 2002 Nov;310(2):169-75. doi: 10.1007/s00441-002-0628-6. Epub 2002 Aug 27.
Unlike most other mammalian cells, beta-cells of Langerhans constitutively express cyclooxygenase (COX)-2 rather than COX-1. COX-2 is also constitutively expressed in type 1 diabetes (T1D) patients' periphery blood monocytes and macrophage. To understand the role of COX-2 in the beta-cell, we investigated COX-2 expression in beta-cells and islet infiltrates of NOD and BALB/c mice using fluorescence immunohistochemistry and cytochemical confocal microscopy and Western blotting. Immunostaining showed that COX-2 is expressed in islet-infiltrating macrophages, and that the expression of insulin and COX-2 disappeared concomitantly from the beta-cells when NOD mice progressed toward overt diabetes. Also cultured INS-1E cells coexpressed insulin and COX-2 but clearly in different subcellular compartments. Treatment with celecoxib increased insulin release from these cells in a dose-dependent manner in glucose concentrations ranging from 5 to 17 mM. Excessive COX-2 expression by the islet-infiltrating macrophages may contribute to the beta-cell death during insulitis. The effects of celecoxib on INS-1E cells suggest that PGE(2) and other downstream products of COX-2 may contribute to the regulation of insulin release from the beta-cells.
与大多数其他哺乳动物细胞不同，胰岛β细胞组成性表达环氧化酶（COX）-2而非COX-1。COX-2也在1型糖尿病（T1D）患者的外周血单核细胞和巨噬细胞中组成性表达。为了解COX-2在β细胞中的作用，我们使用荧光免疫组织化学、细胞化学共聚焦显微镜和蛋白质印迹法，研究了NOD和BALB/c小鼠β细胞及胰岛浸润细胞中COX-2的表达。免疫染色显示，COX-2在胰岛浸润巨噬细胞中表达，并且当NOD小鼠发展为明显糖尿病时，β细胞中的胰岛素和COX-2表达同时消失。同样，培养的INS-1E细胞共表达胰岛素和COX-2，但明显位于不同的亚细胞区室。在5至17 mM的葡萄糖浓度范围内，塞来昔布处理以剂量依赖的方式增加了这些细胞的胰岛素释放。胰岛浸润巨噬细胞中COX-2的过度表达可能在胰岛炎期间导致β细胞死亡。塞来昔布对INS-1E细胞的作用表明，前列腺素E2（PGE2）和COX-2的其他下游产物可能参与β细胞胰岛素释放的调节。
