Impaired salivary gland function in NOD mice - Association with changes in cytokine profile but not with histopathologic changes in the salivary gland
Impaired salivary gland function in NOD mice - Association with changes in cytokine profile but not with histopathologic changes in the salivary gland
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DOI：
10.1002/art.21945
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发表时间：
2006-07-01
影响因子：
--
通讯作者：
Skarstein, Kathrine
中科院分区：
文献类型：
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作者：
Jonsson, Malin V.;Delaleu, Nicolas;Skarstein, Kathrine
objective.描述干燥综合征（SS）模型NOD小鼠的时间病程以及唾液腺炎症、唾液分泌减少和细胞因子水平之间可能的相互关系。不同年龄的NOD小鼠被用来模拟SS的不同疾病阶段。比较了8周龄、17周龄和24周龄雌性小鼠的组织学结果和唾液分泌率。另外，对NOD小鼠和BALB/c小鼠的血清和唾液中的10种细胞因子进行了分析。NOD小鼠唾液流速在8周龄至17周龄之间无明显变化，而在17周龄至24周龄之间显著降低（P <0.001）。相反，在唾液腺的显着的组织病理学变化发生在17周龄之前。慢性炎性细胞浸润以T、B细胞浸润为特征。有趣的是，在三分之一的小鼠中，在局灶性浸润中观察到增殖细胞。随着唾液流量的减少，血清中白细胞介素-2（IL-2）、IL-5和粒细胞-巨噬细胞集落刺激因子的水平以及唾液中IL-4和肿瘤坏死因子α（TNF α）的水平同时发生显著变化。相关性分析显示唾液分泌与NOD小鼠唾液中IL-4、干扰素-γ和TNF α水平呈负相关，而与腺体炎症变化的相关性始终较弱。与以前的研究结果一致，我们的研究结果表明NOD小鼠中至少有2个阶段的SS样疾病。唾液分泌减少之前是唾液腺的炎症变化，而分泌的突然变化发生在炎症没有显著进展的情况下。细胞因子水平的变化是从早期疾病向显性疾病转变的适应性免疫应答中所涉及的机制的指示。
Objective. To characterize the chronologic disease course and possible interrelationships between salivary gland inflammation, hyposalivation, and cytokine levels in NOD mice, a model for Sjogren's syndrome (SS).Methods. NOD mice of different ages were used to mimic different disease stages of SS. Histopathologic findings and rates of salivary secretion were compared between 8-week-old, 17-week-old, and 24-week-old female mice. In addition, 10 cytokines were analyzed in serum and saliva obtained from NOD and BALB/c mice.Results. In NOD mice, the salivary flow rate did not change between 8 weeks and 17 weeks of age, while a significant decrease in the salivary flow rate occurred between 17 weeks and 24 weeks of age (P < 0.001). In contrast, significant histopathologic changes in the salivary glands occurred before 17 weeks of age. Chronic inflammatory cell infiltrates were characterized by T and B cell infiltration. Interestingly, in one-third of the mice, proliferating cells were observed in the focal infiltrates. Significant changes in the levels of interleukin-2 (IL-2), IL-5, and granulocyte-macrophage colony-stimulating factor in serum, and in the levels of IL-4 and tumor necrosis factor alpha (TNF alpha) in saliva occurred contemporarily with the decrease in salivary flow. Correlation analyses revealed a negative association between salivary secretion and the levels of IL-4, interferon-gamma, and TNF alpha in saliva obtained from NOD mice, while the correlation with inflammatory changes in the glands was consistently weak.Conclusion. Consistent with previous findings, our results indicate at least 2 phases of SS-like disease in NOD mice. Hyposalivation was preceded by inflammatory changes in the salivary glands, whereas abrupt changes in secretion occurred without significant progression of inflammation. Changes in cytokine levels are an indication of the mechanisms involved in the adaptive immune response in the transition from early to overt disease.