Ishikawa Larissa Lumi Watanabe, Colavite Priscila Maria, da Rosa Larissa Camargo, Balbino Bianca, França Thais Graziela Donegá, Zorzella-Pezavento Sofia Fernanda Gonçalves, Chiuso-Minicucci Fernanda, Sartori Alexandrina
Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), 18618-000 Botucatu, SP, Brazil.
Biomed Res Int. 2014;2014:148594. doi: 10.1155/2014/148594. Epub 2014 May 27.
Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies.
类风湿性关节炎(RA)是最常见的系统性自身免疫性疾病。它主要影响关节,导致滑膜炎、软骨破坏和骨侵蚀。许多实验模型被用于研究免疫发病机制及该疾病的新疗法。蛋白聚糖诱导的关节炎(PGIA)是一种基于注射的外源(通常是人类)蛋白聚糖与小鼠自身蛋白聚糖的交叉反应性而广泛使用的模型。考虑到人类蛋白聚糖提取和纯化的复杂性,在本研究中,我们评估了市售牛蛋白聚糖的致关节炎性。牛蛋白聚糖具有高度致关节炎性,在雌性BALB/c退休繁殖小鼠中引发了100%的关节炎发生率。用牛蛋白聚糖免疫的动物表现出与人类RA和其他实验模型相似的临床症状和组织病理学特征。此外,与健康小鼠相比,牛蛋白聚糖免疫使关节炎小鼠体内促炎和抗炎细胞因子水平更高。正如预期的那样,只有关节炎组产生了针对蛋白聚糖的IgG1和IgG2a抗体。因此,市售牛蛋白聚糖可作为PGIA的替代抗原来源,用于研究RA的许多方面,包括该疾病的免疫发病机制以及新疗法的开发。