IL 1 INDUCED MONOCYTE CHEMOATTRACTANT PROTEIN: RAT ISLETS IN INSULITIS TYPE I DM

IL 1 诱导的单核细胞趋化蛋白：I 型胰岛素炎中的大鼠胰岛

• 批准号: 6118547
• 负责人: G KWON
• 金额: $ 0.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118547
• 关键词: animal tissue; biological products; biomedical resource; carbohydrates; diabetes mellitus; endocrine gland /system; hormones; immunology; inflammation; lipids; 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-depe ndent 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 islet 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，由于免疫细胞浸润引起的炎症， 是I型糖尿病的标志。 不同 在非肥胖型糖尿病（NOD）患者中观察到胰岛炎的分期 小鼠和BioBreeding（BB）大鼠。 参与的机制 然而，尚不清楚胰岛炎的破坏性进展 明白 在这项研究中，我们研究了细胞因子的作用， 白细胞介素-1（IL-1）刺激胰岛细胞产生 趋化因子，可能在进展中发挥作用， 胰岛炎 IL-1诱导非酯化花生四烯酸的积累 通过同位素稀释质谱法证实胰岛中的酸。 一些花生四烯酸代谢物具有趋化活性。 我们有 观察到从用以下物质处理的大鼠胰岛收集的条件培养基 5 U/ml IL-1对人单核细胞有趋化活性 通过改良的Boyden室测定法测定。 生产 IL-1诱导的胰岛细胞趋化活性呈时间依赖性， 用1（M）放线菌素D处理胰岛完全阻断。此外 大鼠巨噬细胞趋化蛋白-1抗血清 单核细胞趋化蛋白-1（MCP-1）对条件培养液的刺激作用显著抑制单核细胞增殖， 趋化性，表明MCP-1可能部分负责 观察到趋化活性。 我们证实了MCP-1的合成 用原位杂交法检测大鼠胰岛mRNA。 （-胰岛细胞 似乎是MCP-1的来源，因为原代（-）细胞和 胰岛素瘤细胞系RINm 5 F在IL-1活化后表达MCP-1 mRNA。 这些结果表明，胰腺β细胞在IL-1刺激下产生MCP-1， 可能在胰岛炎进展中起作用的激活 与自身免疫性糖尿病有关