期刊
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
卷 35, 期 5, 页码 1309-1316出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2015.2137
关键词
mesenchymal stem cells; transfection; indoleamine 2,3-dioxygenase; immunomodulation; cyclooxygenase-2
资金
- Major State Basic Research Development Program [2012CB966504]
- Shandong Province Natural Science Foundation [ZR2011HM007, 2013GSF11812]
- Shandong University [2012ZD023]
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.
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