Montolio Marta, Téllez Noèlia, Soler Joan, Montanya Eduard
Laboratory of Diabetes and Experimental Endocrinology, Department of Clinical Sciences, University of Barcelona.
Cell Transplant. 2007;16(5):517-25. doi: 10.3727/000000007783464920.
In islet transplantation, local production of cytokines at the grafted site may contribute to the initial nonspecific inflammation response. We have determined whether the metabolic condition of the recipient modulates the cytokine expression in islet grafts in the initial days after transplantation. Normoglycemic and hyperglycemic streptozotocin-diabetic Lewis rats were transplanted with 500 syngeneic islets, an insufficient beta cell mass to restore normoglycemia in hyperglycemic recipients. The expression of IL-1beta, TNF-alpha, IFN-gamma, IL-6, IL-10, and IL-4 genes was determined by real-time PCR in freshly isolated islets, in 24-h cultured islets and in islet grafts on days 1, 3, and 7 after transplantation. IL-1beta mRNA was strongly and similarly increased in normoglycemic and hyperglycemic groups on days 1, 3, and 7 after transplantation compared with freshly isolated and cultured islets. TNF-alpha mRNA was also strongly increased on day 1, and it remained increased on days 3 and 7. IL-6 and IL-10 were not detected in freshly isolated islets, but their expression was clearly enhanced in 24-h cultured islets and islet grafts. IL-6 was further increased in hyperglycemic grafts. IL-10 expression was increased in both normoglycemic and hyperglycemic grafts on day 1 after transplantation, and remained increased in hyperglycemic grafts compared to 24-h cultured islets. IFN-gamma mRNA was barely detected in a few grafts, and IL-4 mRNA was never detected. Thus, the inflammatory response in islet grafts was maximal on day 1 after transplantation, it was sustained, although at lower levels, on days 3 and 7, and it was partly enhanced by hyperglycemia.
在胰岛移植中，移植部位细胞因子的局部产生可能促成最初的非特异性炎症反应。我们已经确定受体的代谢状况是否会在移植后的最初几天调节胰岛移植物中的细胞因子表达。将正常血糖和高血糖链脲佐菌素诱导的糖尿病Lewis大鼠移植500个同基因胰岛，这一胰岛β细胞量不足以使高血糖受体恢复正常血糖水平。通过实时PCR测定新鲜分离的胰岛、培养24小时的胰岛以及移植后第1、3和7天的胰岛移植物中IL-1β、TNF-α、IFN-γ、IL-6、IL-10和IL-4基因的表达。与新鲜分离和培养的胰岛相比，移植后第1、3和7天，正常血糖和高血糖组的IL-1β mRNA均强烈且相似地增加。TNF-α mRNA在第1天也强烈增加，并在第3天和第7天持续增加。新鲜分离的胰岛中未检测到IL-6和IL-10，但它们在培养24小时的胰岛和胰岛移植物中的表达明显增强。高血糖移植物中IL-6进一步增加。移植后第1天，正常血糖和高血糖移植物中IL-10表达均增加，与培养24小时的胰岛相比，高血糖移植物中IL-10表达持续增加。少数移植物中几乎未检测到IFN-γ mRNA，从未检测到IL-4 mRNA。因此，胰岛移植物中的炎症反应在移植后第1天最大，在第3天和第7天持续存在，尽管水平较低，并且高血糖会部分增强这种炎症反应。
