Korani Shahla, Kazemi Bahram, Haghighi Adel, Nikpoor Amin Reza, Bandehpour Mojgan
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Biotechnol. 2019 Jan 11;17(1):e2153. doi: 10.21859/ijb.2153. eCollection 2019 Jan.
The tumor necrosis factor alpha (TNFα) is a cytokine that produced principally by monocyte/macrophages and T lymphocytes, respectively. TNFα is recognized as the primary mediator of immunity in inflammation reaction. One important application of Tumor Necrosis Factor Receptor 2 (TNFR2) is for the treatment of autoimmune diseases like rheumatoid arthritis (RA).
The aim of this study is to examine the therapeutic trace of the recombinant humanTNFR2 on collagen-induced arthritis (CIA) in mice.
CIA was created in 20 mice by immunization with bovine type II collagen (CII). After the mice were boosted on day 21, they were injected with the recombinant protein in test group (1 mg.kg-1) and assessed edema in paws and knee joints after two weeks. The quantities of inflammatory cytokines such as TNF-α, interleukin-1 beta (IL-β1), interleukin-6 (IL-6), and interleukin-10(IL-10) in serum were evaluated through enzyme-linked immunosorbent assay (ELISA) kit. In addition, the histopathology of joints sections was analyzed.
The cytokines TNF-α, IL-1β, and IL-6 values in serum markedly decreased in groups treated with TNFR2 (P < 0.01-0.001). The results showed that treatment with TNFR2 significantly reduced edema in paws and joints (P < 0.01-0.001).
Pathological investigations proved that administration of recombinant TNF receptor has blocked or protected joints from progressive damage. This study suggests that the anti-arthritic effectiveness of TNFR2 will repress the symptoms of rheumatoid arthritis. Moreover, it seems that TNFR2 is a strong candidate for the treatment of the RA disease.
肿瘤坏死因子α（TNFα）是一种主要分别由单核细胞/巨噬细胞和T淋巴细胞产生的细胞因子。TNFα被认为是炎症反应中免疫的主要介质。肿瘤坏死因子受体2（TNFR2）的一个重要应用是用于治疗类风湿性关节炎（RA）等自身免疫性疾病。
本研究的目的是检测重组人TNFR2对小鼠胶原诱导性关节炎（CIA）的治疗效果。
通过用牛II型胶原（CII）免疫20只小鼠制备CIA。在第21天对小鼠进行加强免疫后，给试验组注射重组蛋白（1mg·kg-1），并在两周后评估爪和膝关节的水肿情况。通过酶联免疫吸附测定（ELISA）试剂盒评估血清中炎症细胞因子如TNF-α、白细胞介素-1β（IL-β1）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）的量。此外，分析关节切片的组织病理学。
用TNFR2治疗的组中血清细胞因子TNF-α、IL-1β和IL-6的值显著降低（P<0.01-0.001）。结果表明，用TNFR2治疗可显著减轻爪和关节的水肿（P<0.01-0.001）。
病理研究证明，给予重组TNF受体可阻止或保护关节免受进行性损伤。本研究表明，TNFR2的抗关节炎有效性将抑制类风湿性关节炎的症状。此外，TNFR2似乎是治疗RA疾病的有力候选药物。
