P2X7 receptor knockout prevents streptozotocin-induced type 1 diabetes in mice

被引：29

作者：

Vieira, Flayia Sarmento ^{[1
]}

Nanini, Hayandra Ferreira ^{[1
]}

Takiya, Christina Maeda ^{[2
]}

Coutinho-Silva, Robson ^{[1
]}

机构：

[1] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Imunofisiol, BR-21941 Rio De Janeiro, Brazil

[2] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Patol Clin, BR-21941 Rio De Janeiro, Brazil

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2016年 / 419卷 / 0C期

关键词：

P2X7; receptor; Type; 1; diabetes; eATP; Islet of Langerhans; PANCREATIC BETA-CELLS; NITRIC-OXIDE; AUTOIMMUNE-DISEASE; INSULIN-SECRETION; MOUSE PANCREAS; T-CELLS; ISLET; PATHOGENESIS; INFLAMMATION; PROGRESSION;

D O I：

10.1016/j.mce.2015.10.008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Type 1 diabetes (T1D) is caused by autoimmune destruction of islet of Langerhans beta-cells. P2X7 receptors (P2X7R) modulate proinflammatory immune responses by binding extracellular ATP, a classic 'danger signal'. Here, we evaluated whether the P2X7R has a role in T1D development. P2X7(-/-) mice are resistant to TD1 induction by streptozotocin (STZ) treatment, with no increase in blood glucose, decrease in insulin-positive cells, and pancreatic islet reduction, compared to WT (C57BL/6) mice. Also, the levels of proinflammatory mediators (IL-1 beta, IFN-gamma and NO) did not increase after STZ treatment in P2X7(-/-) animals, with reduced infiltration of CD4(+), CD8(+), B220(+), CD11b(+) and CD11c(+) cells in the pancreatic lymph nodes. Treatment with a P2X7 antagonist mimicked the effect of P2X7 knockout, preventing STZ-induced diabetes. Our results show that the absence of the P2X7R provides resistance in the induction of diabetes in this model, and suggest that therapy targeting the P2X7R may be useful against clinical T1D. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：148 / 157

页数：10

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