Montolio Marta, Biarnés Montse, Téllez Noèlia, Escoriza Jessica, Soler Joan, Montanya Eduard
Institut d'Investigació Biomèdica de Bellvitge, Endocrine Unit, Hospital Universitari de Bellvitge, Barcelona, Spain.
J Endocrinol. 2007 Jan;192(1):169-77. doi: 10.1677/joe.1.06968.
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.
在移植后的最初几天，胰岛特别脆弱，此时细胞死亡会导致超过一半的移植胰岛组织丧失。为了确定由炎症细胞因子的局部表达介导的移植部位的非特异性炎症是否会对移植胰岛的初始损伤产生影响，我们研究了同基因胰岛移植后白细胞介素-1β（IL-1β）和诱导型一氧化氮合酶（iNOS）的表达。用胰岛素治疗的链脲佐菌素诱导糖尿病的Lewis大鼠接受了500个同基因胰岛移植。在移植后1、3或7天收获移植物，通过逆转录聚合酶链反应（RT-PCR）测定IL-1β和iNOS基因的表达。IL-1β和iNOS mRNA在胰岛分离后立即被检测到，并且在移植后上调。IL-1β mRNA在第1天增加了9倍，在移植后第3天仍增加了7倍，并在第7天降至移植前水平。iNOS mRNA显示出与IL-1β相似的表达模式：在移植后第1天和第3天，它分别比新鲜分离的胰岛高14倍和4倍。此外，在胰岛移植物中鉴定出IL-1β和iNOS，发现它们主要由CD68阳性巨噬细胞产生。还鉴定出少量IL-1β和iNOS阳性但CD68阴性的细胞，这表明除巨噬细胞外，其他细胞类型也参与了胰岛移植物中IL-1β的表达和一氧化氮（NO）的产生。胰岛移植后最初几天IL-1β和iNOS基因表达增加以及移植物中存在IL-β和iNOS蛋白的发现证实了胰岛移植后存在早期非特异性炎症反应。总体而言，数据表明IL-1β在胰岛移植后最初几天发现的广泛β细胞死亡中起作用。
