IL-27 Inhibits Hyperglycemia and Pancreatic Islet Inflammation Induced by Streptozotocin in Mice
IL-27 Inhibits Hyperglycemia and Pancreatic Islet Inflammation Induced by Streptozotocin in Mice
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DOI：
10.1016/j.ajpath.2011.08.001
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发表时间：
2011-11-01
影响因子：
6
通讯作者：
Node, Koichi
中科院分区：
文献类型：
--
作者：
Fujimoto, Hirokazu;Hirase, Tetsuaki;Node, Koichi
由免疫细胞和促炎细胞因子驱动的炎症参与了胰岛β细胞损伤，导致糖尿病的发生。IL-27是一种由IL-27p28和EB病毒诱导基因3(EBI3)组成的细胞因子，它与由IL-27受体α链(WSX-1)和gp130组成的膜结合异二聚体受体结合。IL-27具有抗炎作用，可调节T细胞极化和细胞因子的产生。我们评估了链脲佐菌素(STZ)处理的野生型(WT)、EBI3(-/-)和WSX-1(-/-)小鼠的血糖和胰岛胰岛素原浓度、胰岛炎症细胞浸润和IL-1βmRNA的表达。与WT小鼠相比，EBI3(-/-)和WSX-1(-/-)小鼠的高血糖水平升高。经STZ治疗后，EBI3(-/-)和WSX-1(-/-)小鼠的胰岛胰岛素原水平低于WT小鼠。与WT小鼠相比，EBI3(-/-)和WSX-1(-/-)小鼠F4/80(+)CD11c(-)7/4(-)巨噬细胞、CD4(+)T细胞和CD8(+)T细胞对胰岛的浸润增加。与对照组相比，重组IL-27可降低WT和EBI3(-/-)小鼠的血糖水平，降低胰岛免疫细胞浸润，降低胰岛IL-1βmRNA表达，升高胰岛胰岛素原水平。因此，IL-27抑制STZ诱导的小鼠高血糖和胰岛炎症，为糖尿病的β细胞保护提供了一种潜在的新的治疗方法。(Am J Pathol 2011,179：2327-2336.Doi：10.1016/j.ajpath.2011.08.001)
Inflammation driven by immune cells and pro-inflammatory cytokines is implicated in pancreatic beta-cell injury, leading to the development of diabetes mellitus. IL-27, a cytokine consisting of IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3), binds a membrane-bound heterodimeric receptor consisting of the IL-27 receptor alpha chain (WSX-1) and gp130. IL-27 has anti-inflammatory properties that regulate T-cell polarization and cytokine production. We evaluated blood glucose and islet proinsulin concentrations, inflammatory cell infiltration in islets, and expression of IL-1 beta mRNA in pancreas in wild-type (WT), EBI3(-/-), and WSX-1(-/-) mice treated with streptozotocin (STZ). Hyperglycemia was augmented in EBI3(-/-) and WSX-1(-/-) mice compared with WT mice. Islet proinsulin levels after STZ treatment were lower in EBI3(-/-) and WSX-1(-/-) mice than in WT mice. The infiltration of islets by F4/80(+)CD11c(-)7/4(-) macrophages, CD4(+) T cells, and CD8(+) T cells was increased in EBI3(-/-) and WSX-1(-/-) mice compared with WT mice. The administration of recombinant IL-27, compared with control, decreased the blood glucose level, immune cell infiltration into islets, and IL-1 beta mRNA expression in the pancreas and increased islet proinsulin levels in WT and EBI3(-/-) mice. Thus, IL-27 inhibits STZ-induced hyperglycemia and pancreatic islet inflammation in mice and represents a potential novel therapeutic approach for beta-cell protection in diabetes. (Am J Pathol 2011, 179:2327-2336. DOI: 10.1016/j.ajpath.2011.08.001)