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1.
Autoimmunity ; 42(5): 424-31, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19811259

ABSTRACT

Islet transplantation is considered a therapeutic option for type 1 diabetes (T1D). However, allorejection is one major barrier for the successful islet transplantation. In the present study, we have tested the feasibility of a deletion construct for Fas-associated death domain protein (FADD; without the death effecter domain) fused with green fluorescent protein (FADDdel-GFP) for blocking the Fas-FasL signaling pathway in prevention of transplanted beta cell destruction by allo-rejection in T1D. In vitro studies have shown that NIT-1 cells with ectopic FADDdel expression were resistant to cytokine-induced apoptosis and CTL-mediated lysis. Diabetic Balb/c mice reached normoglycemia promptly and gained weight after transplantation of NIT-1 cells with ectopic FADDdel-GFP expression. These recipients showed a significant longer survival time than that of recipients transplanted with NIT cells with ectopic GFP expression only. Our results together suggest that FADDdel could be a useful target for the improvement of islet transplantation for T1D.


Subject(s)
Diabetes Mellitus, Experimental , Fas-Associated Death Domain Protein , Green Fluorescent Proteins , Insulinoma/metabolism , Islets of Langerhans Transplantation/methods , Recombinant Fusion Proteins , Animals , Apoptosis , Diabetes Mellitus, Experimental/therapy , Fas Ligand Protein/antagonists & inhibitors , Fas-Associated Death Domain Protein/genetics , Fas-Associated Death Domain Protein/metabolism , Fas-Associated Death Domain Protein/therapeutic use , Female , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Green Fluorescent Proteins/therapeutic use , Insulinoma/genetics , Mice , Mice, Inbred BALB C , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Recombinant Fusion Proteins/therapeutic use , Sequence Deletion , Transfection , Treatment Outcome , Tumor Cells, Cultured , fas Receptor/antagonists & inhibitors
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