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; 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，由于免疫细胞浸润而引起的炎症和 周围胰岛周围，是I型糖尿病的标志。 不同的 在非肥胖糖尿病（NOD）中已经观察到胰岛炎阶段 小鼠和生物培养（BB）大鼠。 涉及的机制 然而，胰岛炎的破坏性进展并不清楚 理解。 在这项研究中，我们检查了细胞因子的作用 刺激胰岛细胞中的Interluekin-1（IL-1）产生A 趋化因子可能在 胰岛炎。 IL-1诱导非 - =酯化的蛛网膜的积累 同位素稀释质谱法证明，胰岛中的酸。 一些蛛形代谢产物具有趋化活性。 我们有 观察到从用大鼠胰岛收集的条件培养基 5个单位/ml IL-1包含人类单核细胞的趋化活性 由修改的Boyden商会测定法确定。 生产 暴露于IL-1的胰岛趋化活性 延伸时间末端，并通过用1处理胰岛完全阻塞（M 放线霉素D.添加针对大鼠巨噬细胞的抗血清 对条件培养基的化学吸引蛋白1（MCP-1）显着 抑制的单核细胞趋化性，表明MCP-1可能部分 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。 （iStet的细胞似乎是MCP-1的来源 （ - 细胞和胰岛素瘤细胞系RINM5F，Express MCP-1 mRNA IL-1激活。 这些结果表明胰腺（-cells 在IL-1激活时产生MCP-1，可能在 与自身免疫性糖尿病有关的胰岛炎的进展。