Islet primary nonfunction (PNF) is defined as the loss of islet function after transplantation for reasons other than graft rejection. It is a major obstacle to successful and efficient islet transplantation. @entity70543 /TR6 is a soluble death decoy receptor belonging to the @entity5 @entity39 factor (TNF) receptor family, and it can block apoptosis mediated by several TNF receptor family members such as Fas and @entity29956 . In this study, we used TR6 to protect islets from PNF after transplantation. Untreated isogeneic or allogeneic islet transplantation had PNF incidence of 25 and 26.5%, respectively. Administration of TR6 totally prevented PNF in allogeneic islet transplantation. In vitro experiments showed an increased apoptosis among islets that were treated with @entity9699 and @entity60 ( @entity60 ) in combination. TR6 significantly reduced such apoptosis. Functional study showed that insulin release was compromised after @entity9699 and @entity60 treatment, and the compromise could be prevented with TR6-Fc. This indicates that TR6 indeed protected beta-cells from damage caused by @entity9699 and @entity60 . Further in vivo experiments showed that syngeneic islet transplantation between lpr/lpr and gld/gld @entity19 was significantly more efficacious than that conducted between wild-type @entity19 . These results suggest that Fas-mediated apoptosis plays an important role in PNF, and use of TR6 may be a novel strategy to prevent PNF in clinical islet transplantation.

XXXX /TR6 effectively prevents islet primary nonfunction after transplantation.

@entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity70543 :: ('497118(Tax:10090)', 'Gene') :: ['DcR3'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity60 :: ('15978(Tax:10090)', 'Gene') :: ['gamma-interferon', 'IFN-gamma'] @entity9699 :: ('14103(Tax:10090)', 'Gene') :: ['FasL'] @entity29956 :: ('17000(Tax:10090)', 'Gene') :: ['LT beta R']
@entity70543 :: (497118(Tax:10090),Gene) :: ['DcR3']
