title: Overexpression of COX-2 but not indoleamine 2,3-dioxygenase-1 enhances the immunosuppressive ability of human umbilical cord-derived mesenchymal stem cells.
abstract: 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 (IDO-1) and cyclooxygenase-2 (COX-2) genes enhanced the immunosuppressive functional ability of MSCs following stable transfection. To strengthen the immunomodulatory ability of MSCs, IDO-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 cyto-toxicity 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-γ and tumor necrosis factor-α (TNF-α) 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-α-stimulated gene/protein-6, transforming growth factor-β (TGF-β), 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.
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Fu
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Cryomedicine Laboratory, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Ju
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D056747:Immunomodulation / Q000235:genetics; D016130:Immunophenotyping; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D014162:Transfection; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D016207:Cytokines; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D051546:Cyclooxygenase 2