标题：Overexpression of COX-2 but not indoleamine 2,3-dioxygenase-1 enhances the immunosuppressive ability of human umbilical cord-derived mesenchymal stem cells
作者：Li, Dong;Han, Yan;Zhuang, Yong;Fu, Jinqiu;Liu, Huan;Shi, Qing;Ju, Xiuli
作者机构：[Li, D] Cryomedicine Laboratory, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Ji'nan, Shandong, 250012, China;[ Han, Y] Cryomedicine Labora 更多
通讯作者地址：[Ju, XL]Shandong Univ, Qilu Hosp, Cryomed Lab, 107 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：International journal of molecular medicine
关键词：mesenchymal stem cells;transfection;indoleamine 2;3-dioxygenase;immunomodulation;cyclooxygenase-2
摘要：Owing to their immunosuppressive properties mesenchymal stem cells (MSCs) are widely applicable in the treatment of autoimmune disease. The aim of this study was to investigate whether the indoleamine 2,3-dioxygenase-1 (ID 0-1) and cyclooxygenase-2 (COX-2) genes enhanced the immunosuppressive functional ability of MSCs following stable transfection. To strengthen the immunomodulatory ability of MSCs, ID 0-1 and COX-2 were overexpressed in umbilical cord progenitor cell-derived MSCs using recombinant plasmids and electroporation. RT-qPCR analysis and western blotting confirmed the expression of IDO-1 and COX-2 in transfected MSCs. Further functional assays in co-culture experiments, including lymphocyte proliferation and cytotoxicity assays showed that COX-2-transfected MSCs possessed more potent immunomodulatory cells than the untreated MSCs, or MSCs transfected with IDO-1. Additionally, synthesis of interferon-gamma and tumor necrosis factor-alpha (TNF-alpha) was significantly inhibited in lymphocytes co-cultured with COX-2-transfected MSCs, which was consistent with changes in immune-related genes in MSCs. An enhanced expression of IDO-1, COX-2, heme-oxygenase-1, inducible nitric-oxide synthase, TNF-alpha-stimulated gene/protein-6, transforming growth factor-beta (TGF-beta), human leukocyte antigen molecule 5 (HLA-G5) and interleukin-10 (IL-10) was identified following COX-2 transfection. We showed that the overexpression of COX-2 enhanced the immunosuppressive function of MSCs. COX-2-modified MSCs more potently inhibited the activation and proliferation of peripheral blood mononuclear cells.