title: Modest effects of Fas-ligand and heme oxygenase-1 double transgenic mouse islets on transplantation outcomes.
abstract: Interactions of Fas with its ligand (FasL) play an important role in the maintenance of immunologic homeostasis and peripheral tolerance. Heme oxygenase-1 (HO-1) is a protein capable of cytoprotection via radical scavenging and apoptosis prevention. The aim of this study was to test whether overexpression of FasL and HO-1 in murine islets resulted in cell protection and improved functional performance after transplantation. We first generated FasL and HO-1 double transgenic mice to investigate the protective effect of transgenic islets on transplantation. Islets were isolated from FasL and HO-1 double transgenic and nontransgenic Balb/c mice, for transplantation of 300 islets under the left kidney capsule of each streptozotocin-diabetic Balb/c mouse. During 6 weeks after transplantation, the blood glucose gradually decreased in recipients of double transgenic and nontransgenic islets. However, the decrease in blood glucose was more pronounced in the former (450 ± 16 mg/dL at day 0 to 302 ± 55 mg/dL at day 42; P = .01) than the latter (468 ± 17 mg/dL at day 0 to 379 ± 71 mg/dL at day 42; P = .24). The areas under the curve of intraperitoneal glucose tolerance tests at 2, 4, and 6 weeks were not significantly different between recipients of double transgenic and nontransgenic islets. The body weight increased in recipients of double transgenic islets (21.1 ± 1.4 g at day 0 to 26.2 ± 0.8 g at day 42; P = .0002) and nontransgenic islets (21.0 ± 1.4 g at day 0 to 25.1 ± 0.4 g at day 42; P = .0448). Our data suggested modest beneficial effects of transgenic islets with FasL and HO-1 overexpression for transplantation.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan. jjuang@adm.cgmh.org.tw
authors.forename: J-H
authors.initials: JH
authors.lastname: Juang
authors.forename: C-F
authors.initials: CF
authors.lastname: Tu
authors.forename: C-H
authors.initials: CH
authors.lastname: Kuo
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D003921:Diabetes Mellitus, Experimental; D053222:Fas Ligand Protein / Q000096:biosynthesis*; D005951:Glucose Tolerance Test; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats
chemical_list: D053222:Fas Ligand Protein; D007328:Insulin; D051547:Heme Oxygenase-1