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首页> 外文学位 >Up-regulation of inflammatory cytokines in the lacrimal glands of a predisposed mouse model of Sjogren's Syndrome (SS): The influence of sex hormones and a newly proposed mechanism for SS.
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Up-regulation of inflammatory cytokines in the lacrimal glands of a predisposed mouse model of Sjogren's Syndrome (SS): The influence of sex hormones and a newly proposed mechanism for SS.

机译：干燥综合征干燥小鼠模型（SS）的泪腺炎性细胞因子的上调：性激素的影响和新提出的SS机制。

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摘要

Sjögren’s Syndrome (SS) is a chronic, inflammatory autoimmune disease affecting mostly the exocrine cells of lacrimal and salivary glands, leading to diminished secretory function and resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease). Despite several decades of studies focusing on autoimmune diseases and dry eye diseases, the exact etiology and mechanisms of SS remain unknown. Besides the fact that SS is often unreported, unrecognized and untreated, today’s therapies rely exclusively on treating the symptoms after disease progression; there exists neither prevention therapy nor cure for SS. In addition, SS has been diagnosed predominantly in post-menopausal women with the female to male ratio reaching 9:1, suggesting a role of ovarian sex hormones in the pathogenesis of SS. However, not all postmenopausal women develop SS, indicating the contribution of other factors such as a genetic background to the onset of SS. In the present study, ovariectomized (OVX) NOD.B10.H2b mice provide a model of menopause with a genetic predisposition to SS, as compared to non-predisposed C57BL/10 mice. Both strands of mice were either sham operated, OVX, OVX and treated with 17β estradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected 3, 7, 21, and 30 days after surgery and processed for RNA analysis by rt-qPCR and protein assays by ELISA to evaluate cytokine expression and concentrations of IL-1β, TNF-α, IFN-γ, IL-10, and IL-4 on a timeline. Overall, our results showed a significant increase in IL-1β, TNF-α, IL-10, and IL-4 expression and levels in the lacrimal glands of OVX NOD.B10.H2b mice as compared to sham operated animals, and treatment with E2 or DHT at time of OVX prevented the increase in cytokine expression and levels. Except for the expression of IL-1β and IL-4, no significant changes in cytokine expression and levels were observed in the lacrimal glands of C57BL/10 mice for all experimental groups. Both expression and levels of IFN-γ remained undetected in both mouse strains for all experimental groups. From this study, we suggest that cytokines are key players in the pathogenesis of SS, and that the specific time frame of up-regulation of each cytokine is crucial to the understanding of the exact disease mechanism. This study further unravels the SS-mechanism, allowing for possible advancement in hormone replacement therapies and cytokine-directed therapies.
机译：干燥综合征（SS）是一种慢性炎症性自身免疫疾病，主要影响泪腺和唾液腺的外分泌细胞，导致分泌功能减弱，并导致干燥性角膜结膜炎和/或干燥性口腔炎。尽管数十年来针对自身免疫性疾病和干眼病的研究，SS的确切病因和机制仍未知。除了SS通常未被报道，未被识别和未经治疗的事实外，今天的疗法还完全依赖于疾病发展后的症状的治疗。既没有预防疗法也没有治愈SS的方法。此外，主要在绝经后的女性中诊断出SS，女性与男性的比例达到9：1，表明卵巢性激素在SS的发病机理中具有重要作用。但是，并非所有绝经后妇女都患有SS，这表明其他因素（例如遗传背景）对SS的发病也有贡献。在本研究中，与非易感性C57BL / 10小鼠相比，去卵巢（OVX）NOD.B10.H2b小鼠提供了具有SS遗传易感性的绝经模型。小鼠的两条链均是假手术的，OVX，OVX并用17β雌二醇（E2）治疗，或OVX并用二氢睾酮（DHT）治疗。在手术后3、7、21和30天收集泪腺，并通过rt-qPCR进行RNA分析，并通过ELISA进行蛋白质分析，以评估细胞因子的表达以及IL-1β，TNF-α，IFN-γ，IL-的浓度。 10，以及时间轴上的IL-4。总体而言，我们的结果显示，与假手术的动物相比，OVX NOD.B10.H2b小鼠的泪腺中IL-1β，TNF-α，IL-10和IL-4的表达和水平显着增加， OVX时E2或DHT阻止了细胞因子表达和水平的增加。除了IL-1β和IL-4的表达外，对于所有实验组，在C57BL / 10小鼠的泪腺中均未观察到细胞因子表达和水平的显着变化。对于所有实验组，在两种小鼠品系中均未检测到IFN-γ的表达和水平。从这项研究中，我们建议细胞因子是SS发病机理的关键因素，并且每种细胞因子上调的特定时间范围对于理解确切的疾病机制至关重要。这项研究进一步阐明了SS机制，从而可能在激素替代疗法和细胞因子定向疗法中取得进展。

著录项

  • 作者

    Czerwinski, Stefanie P.C.;

  • 作者单位

    Florida Atlantic University.;

  • 授予单位 Florida Atlantic University.;
  • 学科 Health Sciences Ophthalmology.;Health Sciences Immunology.;Biology Endocrinology.
  • 学位 M.S.
  • 年度 2013
  • 页码 57 p.
  • 总页数 57
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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