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Experimental Models of Arthritis in Which Pathogenesis Is Dependent on TNF Expression

机译:发病机制取决于TNF表达的关节炎实验模型

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Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by joint damage as well as systemic manifestations. The exact cause of RA is not known. Both genetic and environmental factors are believed to con-tribute to the development of this disease. Increased expression of tumor necrosis factor (TNF) has been implicated in the pathogenesis of RA. Currently, the use of anti-TNF drugs is one of the most effective strategies for the treatment of RA, although therapeutic response is not observed in all patients. Furthermore, due to non-redundant protective functions of TNF, systemic anti-TNF therapy is often associated with unwanted side effects such as increased frequency of infectious diseases. Development of experimental models of arthritis in mice is necessary for studies on the mechanisms of pathogenesis of this disease and can be useful for comparative evaluation of various anti-TNF drugs. Here we provide an overview of the field and present our own data with two experimental models of autoimmune arthritis - collagen-induced arthritis and antibody-induced arthritis in C57Bl/6 and BALB/c mice, as well as in tnf-humanized mice generated on C57Bl/6 back-ground. We show that TNF-deficient mice are resistant to the development of collagen-induced arthritis, and the use of anti-TNF therapy significantly reduces the disease symptoms. We also generated and evaluated a fluorescent detector of TNF overexpression in vivo. Overall, we have developed an experimental platform for studying the mechanisms of action of existing and newly developed anti-TNF drugs for the treatment of rheumatoid arthritis.
机译:类风湿关节炎(RA)是一种自身免疫性炎性疾病,其特征在于关节损伤以及全身性表现。 RA的确切原因尚不清楚。遗传和环境因素都被认为有助于该疾病的发展。肿瘤坏死因子(TNF)的表达增加与RA的发病机制有关。目前,尽管未在所有患者中观察到治疗反应,但抗TNF药物的使用是治疗RA最有效的策略之一。此外,由于TNF的非冗余保护功能,全身性抗TNF疗法通常与不良副作用如传染病的发生频率增加有关。为了研究这种疾病的发病机理,必须建立小鼠关节炎实验模型,这对于各种抗TNF药物的比较评价是有用的。在这里,我们提供了该领域的概述,并用两种自身免疫性关节炎的实验模型展示了我们自己的数据-C57Bl / 6和BALB / c小鼠,以及在C57Bl / 6和BALB / c小鼠中胶原诱导的关节炎和抗体诱导的关节炎C57Bl / 6背景。我们表明,TNF缺陷型小鼠对胶原蛋白诱发的关节炎的发展有抵抗力,并且抗TNF疗法的使用显着减轻了疾病症状。我们还生成并评估了体内TNF过表达的荧光检测器。总的来说,我们已经开发了一个实验平台,用于研究现有和新开发的抗TNF药物治疗类风湿关节炎的作用机理。

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