The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes.
The involvement of interleukin-22 in the expression of pancreatic beta cell regenerative Reg genes.
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DOI：
10.1186/2045-9769-2-2
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Singh B
中科院分区：
文献类型：
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作者：
Hill T;Krougly O;Nikoopour E;Bellemore S;Lee-Chan E;Fouser LA;Hill DJ;Singh B
在1型糖尿病中，朗格汉斯胰岛内产生胰岛素的β细胞被破坏。我们之前的研究表明，用卡介苗（BCG）或完全弗氏佐剂（CFA）免疫治疗非肥胖糖尿病（NOD）小鼠可以预防疾病进程和胰腺β细胞损失。这与胰岛再生（regg）基因表达增加和胰腺中产生il -22的Th17 t细胞升高有关。我们假设IL-22是胰腺中Reg基因表达增加的原因。因此，我们量化了IL-22处理的离体糖尿病前期NOD胰岛中Reg1、Reg2和Reg3δ (INGAP) mRNA的表达。我们测量了IL-22和IL-22受体(R)-α mRNA在糖尿病前期和糖尿病NOD小鼠胰腺和脾脏中的表达。结果表明：1)il -22处理的胰岛细胞Reg1和Reg2 mRNA丰度显著升高；2) CFA治疗后，糖尿病前期小鼠胰腺IL-22 mRNA表达随时间增加而升高；3) CFA治疗后IL-22Rα表达降低；4)注射IL-22中和抗体可下调糖尿病前期小鼠胰腺中Reg1和Reg2 mRNA的表达；5)在IL-22存在的情况下，胰岛β细胞DNA合成增加。我们得出结论，IL-22可能通过上调胰岛再生Reg1和Reg2基因来促进β细胞的再生。
In Type 1 diabetes, the insulin-producing β-cells within the pancreatic islets of Langerhans are destroyed. We showed previously that immunotherapy with Bacillus Calmette-Guerin (BCG) or complete Freund’s adjuvant (CFA) of non-obese diabetic (NOD) mice can prevent disease process and pancreatic β-cell loss. This was associated with increased islet Regenerating (Reg) genes expression, and elevated IL-22-producing Th17 T-cells in the pancreas. We hypothesized that IL-22 was responsible for the increased Reg gene expression in the pancreas. We therefore quantified the Reg1, Reg2, and Reg3δ (INGAP) mRNA expression in isolated pre-diabetic NOD islets treated with IL-22. We measured IL-22, and IL-22 receptor(R)-α mRNA expression in the pancreas and spleen of pre-diabetic and diabetic NOD mice. Our results showed: 1) Reg1 and Reg2 mRNA abundance to be significantly increased in IL-22-treated islets in vitro; 2) IL-22 mRNA expression in the pre-diabetic mouse pancreas increased with time following CFA treatment; 3) a reduced expression of IL-22Rα following CFA treatment; 4) a down-regulation in Reg1 and Reg2 mRNA expression in the pancreas of pre-diabetic mice injected with an IL-22 neutralizing antibody; and 5) an increased islet β-cell DNA synthesis in vitro in the presence of IL-22. We conclude that IL-22 may contribute to the regeneration of β-cells by up-regulating Regenerating Reg1 and Reg2 genes in the islets.