IL 1 INDUCED EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN W/ TYPE I DIABETES

IL 1 诱导 I 型糖尿病单核细胞趋化蛋白的表达

• 批准号: 6665849
• 负责人: G KWON
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665849
• 关键词: animal tissue; biological products; biomedical resource; cognition; eye; spectrometry

Insulitis, inflammation due to infiltration of immune cells in and around pancreatic islets, is a hallmark of type I diabetes. Different stages of insulitis have been observed in non-obese diabetic (NOD) mice and BioBreeding (BB) rats. Mechanisms involved in the destructive progression of insulitis, however, are not clearly understood. In this study, we examined the role of the cytokine interluekin-1 (IL-1) in stimulating islet cells to produce a chemotactic factor(s) that may play a role in the progression of insulitis. IL-1 induces accumulation of non-=esterified arachidonic acid in islets as demonstrated by isotope dilution mass spectrometry. Some arachidonate metabolites have chemotactic activity. We have observed that conditioned media collected from rat islets treated with 5 units/ml IL-1 contained chemotactic activities for human monocytes determined by modified Boyden chamber assays. The production of chemotactic activity by islets exposed to IL-1 was time-dep endent and completely blocked by treating islets with 1(M actinomycin D. Addition of antiserum raised against rat macrophage chemoattractant protein-1 (MCP-1) to conditioned media significantly inhibited monocyte chemotaxis, suggesting that MCP-1 may, in part, be responsible for the chemotactic activity observed. We confirmed the synthesis of MCP-1 mRNA by rat islets using in situ hybridization. (-cells of the istlet appear to be the source of MCP-1 since primary (-cells and the insulinoma cell line, RINm5F, express MCP-1 mRNA upon IL-1 activation. These results indicate that pancreatic (-cells produce MCP-1 upon IL-1 activation that may play a role in the progression of insulitis associated with autoimmune diabetes.

胰岛炎，由于免疫细胞浸润和 胰岛周围，是 I 型糖尿病的标志。 不同的 在非肥胖糖尿病 (NOD) 中观察到了胰岛素炎的各个阶段 小鼠和生物育种 (BB) 大鼠。 涉及的机制 然而，胰岛素炎的破坏性进展尚不清楚 明白了。 在这项研究中，我们检查了细胞因子的作用 白细胞介素-1 (IL-1) 刺激胰岛细胞产生 可能在病情进展中发挥作用的趋化因子 胰岛炎。 IL-1 诱导非酯化花生四烯酸的积累 同位素稀释质谱法证明了胰岛中的酸。 一些花生四烯酸代谢物具有趋化活性。 我们有 观察到从经过处理的大鼠胰岛收集的条件培养基 5 单位/ml IL-1 对人单核细胞具有趋化活性 通过改良的博伊登室测定法测定。 生产 暴露于 IL-1 的胰岛的趋化活性 通过用 1(M 放线菌素 D. 添加针对大鼠巨噬细胞的抗血清 趋化蛋白-1 (MCP-1) 对条件培养基的影响显着 抑制单核细胞趋化性，表明 MCP-1 可能部分是 负责观察到的趋化活性。 我们确认了 使用原位杂交通过大鼠胰岛合成 MCP-1 mRNA。 （-自初级以来，胰岛细胞似乎是 MCP-1 的来源 （-细胞和胰岛素瘤细胞系 RINm5F 在 IL-1 激活。 这些结果表明胰腺（-细胞 IL-1 激活后产生 MCP-1，可能在 与自身免疫性糖尿病相关的胰岛素炎的进展。