炎性细胞因子对人胚胎胰岛功能及其分泌IL_6的调控效应

The regulatory effects of immunoinflammatory cytokines on human fetal pancreatic islet function and IL 6 production

目的 探讨正常人胚胎胰岛在 Ｉ Ｌ１β、 Ｔ Ｎ Ｆα、 Ｉ Ｆ Ｎγ作用下， Ｉ Ｌ６ 的分泌及基因表达状况。方法 采用常规消化方法分离人胚胎胰岛并进行培养，分别加入ｒｈ Ｉ Ｌ１β、ｒｈ Ｔ Ｎ Ｆα、ｒｈ Ｉ Ｆ Ｎγ或同时加入２ 种或３ 种细胞因子，作用２４ 、４８ 小时收上清，进行 Ｉ Ｌ６ 、胰岛素、胰高血糖素活性检测和 Ｉ Ｌ６单抗中和实验，同时对３ 种细胞因子联合刺激的胰岛 Ｒ Ｎ Ａ 进行 Ｉ Ｌ６ ｍ Ｒ Ｎ Ａ 斑点杂交。结果 ３ 种细胞因子单独或联合刺激均可大幅度提高 Ｉ Ｌ６ 和胰高血糖素的分泌，同时不同程度地抑制胰岛素的分泌，细胞因子刺激胰岛的时间和强度与 Ｉ Ｌ６ 、胰岛素、胰高血糖素的分泌有明显的关系。斑点杂交结果显示３ 种细胞因子联合刺激的胰岛 Ｒ Ｎ Ａ 中 Ｉ Ｌ６ ｍ Ｒ Ｎ Ａ 含量明显高于对照组。结论 炎性细胞因子调节胰岛分泌 Ｉ Ｌ６ 和 Ｉ Ｌ６ 基因表达。

The regulatory effects of immunoinflammatory cytokines on human fetal pancreatic islet function and IL6 production$$$$ TIAN Zhigang, SUN Rui, ZHANG Jianhua, et al. Shandong Cancer Biotherapy Center, Shandong Academy of Medical Sciences, Jinan 250062 【 Abstract 】 Objective To study the immunoinflammatory cytokine effects on fetal pancreatic islet function and IL6 production in vitro. Methods The islets from fetal pancreas were separated by collagenase type V (0.5mg/ml) and cultured in vitro. The islets were exposed to culture medium alone or with different kinds of inflammatory cytokines for 24 or 48 h 〔rhIL1β (10U/ml), rhTNFα(100U/ml), rhIFNγ(250U/ml)〕. The supernatants of culture of human fetal islets were assayed for the concentrations of IL6, insulin and glucagon. Results The results showed that (1) IL6 activity of all groups was significantly increased when islets were exposed to immunoinflammatory cytokines. (2) IL6 McAb significantly reduced the IL6 activity in islet supernatants from control group or experiment groups. (3) IL6 mRNA in human fetal islets exposed to immunoinflammatory cytokines was higher than that of control in dot hybridization. (4) Insulin secretion of all groups was inhibited to different degrees after islets were exposed to inflammatory cytokine(s) alone or with different combinations. (5) Glucagon secretion of all groups was significantly increased after exposure to the immunoinflammatory cytokines. Conclusion The results suggest that pancreatic islets producing IL6 is upregulated by immunoinflammatory cytokines. 【 Subject words 】 Fetal Islet IL6 rhIL1β rhTNFα rhIFNγ