Islet inflammation and hyperplasia induced by the pancreatic islet-specific overexpression of interleukin-6 in transgenic mice.
Islet inflammation and hyperplasia induced by the pancreatic islet-specific overexpression of interleukin-6 in transgenic mice.
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发表时间：
1994-07
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通讯作者：
lain L. Campbell;Monte V. Hobbs;J. Dockter;Michael B. A. Oldstone;Janette Allisont
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作者：
lain L. Campbell;Monte V. Hobbs;J. Dockter;Michael B. A. Oldstone;Janette Allisont
白细胞介素-6（IL-6）被认为参与了自身免疫性胰岛素依赖型糖尿病的发病机制。为了检验这种可能性，我们开发了两种在胰岛β细胞中过表达IL-6的转基因小鼠（称为RIP-IL 6）。RIP-IL 6小鼠，虽然显示出适度的体重减轻，但在其一生中保持血糖正常。此外，胰岛素基因表达和葡萄糖耐量与非转基因同窝仔相似。组织学检查显示RIP-IL 6动物的胰腺而非其他器官发生显著变化，胰岛结构、胰岛细胞和周围组织发生显著改变。在年轻动物中，这些变化包括胰岛增生伴有丝分裂相增加、新导管形成、纤维化和少量单核细胞浸润（胰岛炎）。此外，胰岛激素的免疫染色揭示了β和α细胞的拓扑结构和密度的变化。在老年RIP-IL 6小鼠中，观察到更丰富的胰岛炎，其主要由B220+ B淋巴细胞组成，并且在较小程度上由Mac-1+巨噬细胞和CD 4+和CD 8 + T淋巴细胞组成。小鼠IgG免疫染色显示胰岛周围浸润物中有大量浆细胞，这表明IL-6诱导了募集的B淋巴细胞的分化。因此，IL-6的胰岛过表达产生复杂的、局部的宿主应答，这不仅涉及在自身免疫性糖尿病中发生的炎症过程，而且涉及细胞新生，这可能表明在组织修复中的作用。
Interleukin-6 (IL-6) is thought to be involved in the pathogenesis of autoimmune insulin-dependent diabetes mellitus. To examine this possibility, we developed two lines of transgenic mice (termed RIP-IL6) which overexpressed IL-6 in the pancreatic islet beta cells. RIP-IL6 mice, while showing a modest reduction in body weight, remained normoglycemic throughout their lives. Furthermore, insulin gene expression and glucose tolerance were similar to non-transgenic littermates. Histopathological examination revealed significant changes in the pancreas but not other organs of RIP-IL6 animals, with marked alterations in the architecture of the islets, in the islet cells, and in surrounding tissues. In younger animals these changes included islet hyperplasia with increased mitotic figures, neo-ductular formation, fibrosis, and a scant mononuclear cell infiltration (insulitis). In addition, immunostaining for islet hormones revealed changes in both the topography and density of beta and alpha cells. In older RIP-IL6 mice, a more florid insulitis was observed which was composed predominantly of B220+ B lymphocytes and, to a lesser extent, Mac-1+ macrophages and CD4+ and CD8+ T lymphocytes. Immunostaining for mouse IgG revealed significant numbers of plasma cells in the peri-islet infiltrates, which suggested that IL-6 induced differentiation of the recruited B lymphocytes. Therefore, islet overexpression of IL-6 produces a complex, localized host response implicating this cytokine in not only inflammatory processes that occur in autoimmune diabetes but also cellular neogenesis, which may indicate a role in tissue repair.