title: Interleukin-1beta and inducible form of nitric oxide synthase expression in early syngeneic islet transplantation.
abstract: Islets are particularly vulnerable in the initial days after transplantation when cell death results in the loss of more than half of the transplanted islet tissue. To determine whether a non-specific inflammation at the grafted site mediated by the local expression of inflammatory cytokines could play a role on the initial damage to transplanted islets, we studied the expressions of interleukin-1beta (IL-1beta) and inducible form of nitric oxide synthase (iNOS) after syngeneic islet transplantation. Insulin-treated streptozotocin-diabetic Lewis rats were syngeneically transplanted with 500 islets. Grafts were harvested 1, 3, or 7 days after transplantation, and the expressions of IL-1beta and iNOS genes were determined by RT-PCR. IL-1beta and iNOS mRNAs were detected in islets immediately after isolation, and were upregulated after transplantation. IL-1beta mRNA was ninefold increased on day 1, was still sevenfold increased on day 3 after transplantation, and declined towards pretransplantation levels on day 7. iNOS mRNA showed a similar pattern of expression to that of IL-1beta: on days 1 and 3 after transplantation it was 14-and 4-fold higher respectively than in freshly isolated islets. In addition, IL-1beta and iNOS were identified in islet grafts and found to be produced mainly by CD68-positive macrophages. A low number of IL-1beta- and iNOS-positive but CD68-negative cells were also identified suggesting that other cell types, in addition to macrophages, were involved in the expression of IL-1beta and NO production in islet grafts. The finding of increased IL-1beta and iNOS gene expressions in the initial days after islet transplantation and the presence of IL-beta and iNOS proteins in the graft confirmed the presence of an early non-specific inflammatory response after islet transplantation. Overall, the data suggest that IL-1beta plays a role in the extensive beta-cell death found in the initial days after islet transplantation.
authors.affiliation: Institut d'Investigació Biomèdica de Bellvitge, Endocrine Unit, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Montolio
authors.forename: Montse
authors.initials: M
authors.lastname: Biarnés
authors.forename: Noèlia
authors.initials: N
authors.lastname: Téllez
authors.forename: Jessica
authors.initials: J
authors.lastname: Escoriza
authors.forename: Joan
authors.initials: J
authors.lastname: Soler
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D015870:Gene Expression; D006085:Graft Survival / Q000276:immunology; D007150:Immunohistochemistry / Q000379:methods; D053583:Interleukin-1beta / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008264:Macrophages / Q000276:immunology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014185:Transplantation, Isogeneic; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D053583:Interleukin-1beta; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule