title: Adverse effect on syngeneic islet transplantation by transgenic coexpression of decoy receptor 3 and heme oxygenase-1 in the islet of NOD mice.
abstract: Decoy receptor 3 (DcR3) blocks both Fas ligand- and LIGHT-induced pancreatic β-cell damage in autoimmune diabetes. Heme oxygenase 1 (HO-1) possesses antiapoptotic, anti-inflammatory, and antioxidative effects that protect cells against various forms of attack by the immune system. Previously, we have demonstrated that transgenic islets overexpressing DcR3 or murine HO-1 (mHO-1) exhibit longer survival times than nontransgenic islets in syngeneic islet transplantation. In this study, we evaluated whether DcR3 and mHO-1 double-transgenic islets of NOD mice could provide better protective effects and achieve longer islet graft survival than DcR3 or mHO-1 single-transgenic islets after islet transplantation. We generated DcR3 and mHO-1 double-transgenic NOD mice that specifically overexpress DcR3 and HO-1 in islets. Seven hundred islets isolated from double-transgenic, single-transgenic, or nontransgenic NOD mice were syngeneically transplanted into the kidney capsules of newly diabetic female recipients. Unexpectedly, there was no significant difference in the survival time between double-transgenic or nontransgenic NOD islet grafts, and the survival times of double-transgenic NOD islet grafts were even shorter than those of DcR3 or mHO-1 single-transgenic islets. Our data indicate that transplantation of double-transgenic islets that coexpress HO-1 and DcR3 did not result in a better outcome. On the contrary, this strategy even caused an adverse effect in syngeneic islet transplantation.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: S-H
authors.initials: SH
authors.lastname: Huang
authors.forename: G-J
authors.initials: GJ
authors.lastname: Lin
authors.forename: M-W
authors.initials: MW
authors.lastname: Chien
authors.forename: C-H
authors.initials: CH
authors.lastname: Chu
authors.forename: J-C
authors.initials: JC
authors.lastname: Yu
authors.forename: T-W
authors.initials: TW
authors.lastname: Chen
authors.forename: D-Y
authors.initials: DY
authors.lastname: Hueng
authors.forename: Y-L
authors.initials: YL
authors.lastname: Liu
authors.forename: H-K
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014185:Transplantation, Isogeneic
chemical_list: D008565:Membrane Proteins; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse