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首页> 外文期刊>Clinical and diagnostic laboratory immunology >Chronic administration of dexamethasone results in Fc receptor up-regulation and inhibition of class I antigen expression on macrophages from MRL/lpr autoimmune mice.
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Chronic administration of dexamethasone results in Fc receptor up-regulation and inhibition of class I antigen expression on macrophages from MRL/lpr autoimmune mice.

机译:长期给予地塞米松会导致Fc受体上调并抑制MRL / lpr自身免疫小鼠巨噬细胞上的I类抗原表达。

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The MRL/lpr mouse develops, after approximately 8 weeks of age, a severe autoimmune syndrome with many features resembling human systemic lupus erythematosus, including autoantibodies against DNA and basement membranes resulting in immune complexes, vasculitis, and multiorgan disease. While this murine model of lupus has been used for the identification of therapeutics with potential efficacy in human autoimmune disease, the long-term impact of chronic immunosuppressive therapy on macrophage function in this paradigm is not understood. To this end, MRL/lpr mice were treated prophylactically with dexamethasone at 0.01, 0.1, and 1 mg/kg of body weight for 20 weeks or were allowed to develop autoimmune disease and, at 15 weeks of age, treated therapeutically with 1-mg/kg dexamethasone for 8 additional weeks. Analysis of surface antigens on resident peritoneal macrophages demonstrated a progressive loss in class I expression with a concomitant increase in Fc receptor expression. Neither phagocytosis nor CD11b expression was modulated with chronic steroid treatment. Furthermore, dexamethasone treatment was associated with a reduction in anti-DNA antibodies and total immunoglobulin G and yet an elevation in serum cholesterol due to an increase in high-density lipoproteins. Therefore, the MRL/lpr mouse serves not only as a small-animal model of autoimmune disease but also as one in which the negative and positive sequelae associated with chronic immunosuppression can be further understood.
机译:MRL / lpr小鼠在约8周龄后发展为严重的自身免疫综合症,具有许多类似于人系统性红斑狼疮的特征,包括针对DNA和基底膜的自身抗体,导致免疫复合物,血管炎和多器官疾病。尽管这种狼疮鼠模型已经用于鉴定在人类自身免疫性疾病中具有潜在功效的治疗方法,但尚不了解慢性免疫抑制治疗对巨噬细胞功能的长期影响。为此,对MRL / lpr小鼠进行预防性地塞米松治疗,剂量分别为0.01、0.1和1 mg / kg体重20周,或使其发生自身免疫性疾病,并在15周龄时用1-mg进行治疗/ kg地塞米松另外8周。对驻留的腹膜巨噬细胞上的表面抗原的分析表明,I类表达逐渐丧失,同时Fc受体表达增加。慢性类固醇治疗既不能调节吞噬作用,也不能调节CD11b的表达。此外,地塞米松治疗与抗DNA抗体和总免疫球蛋白G的减少有关,但由于高密度脂蛋白的增加而导致血清胆固醇的增加。因此,MRL / lpr小鼠不仅可以作为自身免疫疾病的小动物模型,而且还可以进一步了解与慢性免疫抑制有关的阴性和阳性后遗症。

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