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

岛炎，因免疫细胞渗入而引起的炎症 在胰岛周围，是I型糖尿病的标志。不同 在非肥胖型糖尿病(NOD)中观察到了不同阶段的胰岛素炎。 小鼠和生物育种(BB)大鼠。参与其中的机制 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，我们研究了细胞因子的作用。 白介素1(IL-1)在刺激胰岛细胞产生 趋化因子(S)，可能在肺癌的进展中发挥作用 胰岛炎症。IL-1诱导非酯化花生四烯酸蓄积 用同位素稀释质谱仪证实了胰岛中的酸。 一些花生四烯酸代谢产物具有趋化活性。我们有 观察到从大鼠胰岛收集的条件培养液 5U/mlIL-1对人单核细胞的趋化活性 用改良的博伊登小室测定法测定。产品的生产 IL-1对胰岛趋化活性的影响 用1(M)处理胰岛可延缓和完全阻断胰岛 放线菌素D在大鼠巨噬细胞抗血清中的添加 趋化蛋白-1(MCP-1)对条件培养液的影响 抑制单核细胞趋化，提示MCP-1可能在一定程度上是 对观察到的趋化活动负责。我们确认了 大鼠胰岛单核细胞趋化蛋白-1mRNA的原位杂交合成 (-istlet的细胞似乎从初级开始就是MCP-1的来源 (-)细胞和胰岛素瘤细胞系RINm5F表达MCP-1mRNA IL-1激活。这些结果表明，胰腺(-)细胞 在IL-1激活时产生MCP-1，可能在 与自身免疫性糖尿病相关的胰岛素炎的进展。

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.