IL 1 INDUCED EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN W/ TYPE I 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 5U/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 暴露于IL-1的胰岛的趋化活性 用1（M）处理胰岛，时间依赖性和完全阻断 放线菌素D添加抗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著 抑制单核细胞趋化性，这表明MCP-1可能，部分， 负责观察到的趋化活性。 我们证实了 大鼠胰岛MCP-1 mRNA合成的原位杂交研究 （-）胰岛细胞似乎是MCP-1的来源， 细胞和胰岛素瘤细胞系RINm5F表达MCP-1 mRNA， IL-1激活。 这些结果表明，胰腺β细胞 在IL-1活化后产生MCP-1，这可能在 与自身免疫性糖尿病相关的胰岛炎的进展。

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.