The effects of Staphylococcus aureus protein a (SpA) on the expression of inflammatory cytokines in autoimmune patients and their probable immune response modulation mechanisms

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine Pub Date : 2024-08-31 DOI:10.1016/j.cyto.2024.156745
Garshasb Rigi , Gholamali Kardar , Abbas Hajizade , Javad Zamani , Gholamreza Ahmadian
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Abstract

The recombinant Staphylococcal protein A (SpA) is widely used in biotechnology to purify polyclonal and monoclonal IgG antibodies. At very low concentrations, the highly-purified form of the protein A can down-regulate the activation of human B-lymphocytes and macrophages which are the key cells in determining autoimmune diseases. In the present study, the efficiency of three different forms of protein A, including native full-length SpA, the recombinant full-length SpA, and a recombinant truncated form of SpA on the reduction of 4 inflammatory cytokines, including IL-8, IL-1β, TNF-α, and IL-6 by peripheral blood mononuclear cell (PBMCs) were studied and compared to an anti-rheumatoid arthritis commercial drug, Enbrel. The recombinant proteins were expressed in E. coli and the native form of SpA was commercially provided. PBMCs were obtained from adult patients with active rheumatoid arthritis (RA) and healthy control donors. Then, the effect of different doses of the three pure forms of SpA in comparison with Enbrel was investigated by analyzing the expression of selected cytokines using ELISA. The results showed that the truncated form of recombinant SpA significantly reduced the expression of cytokines more effectively than the other full-length formulations as well as the commercial drug Enbrel. In silico analysis shows that in the truncated protein, as the radius of gyration increases, the structure of IgG-binding domains become more open and more exposed to IgG. To summarize, our findings indicate that the truncated form of protein A is the most efficient form of SpA as it significantly decreases the secretion of evaluated cytokines from PBMCs in vitro.

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金黄色葡萄球菌蛋白 a (SpA) 对自身免疫性疾病患者炎症细胞因子表达的影响及其可能的免疫反应调节机制
重组葡萄球菌蛋白 A(SpA)在生物技术中被广泛用于纯化多克隆和单克隆 IgG 抗体。在极低浓度下,高纯度的蛋白 A 可以下调人类 B 淋巴细胞和巨噬细胞的活化,而这些细胞是决定自身免疫性疾病的关键细胞。在本研究中,研究了三种不同形式的蛋白 A(包括原生全长 SpA、重组全长 SpA 和重组截短 SpA)对降低外周血单核细胞(PBMCs)的四种炎症细胞因子(包括 IL-8、IL-1β、TNF-α 和 IL-6)的效率,并与抗类风湿性关节炎药物 Enbrel 进行了比较。重组蛋白在大肠杆菌中表达,SpA 的原生形式由市场提供。从活动性类风湿性关节炎(RA)成年患者和健康对照供体中获取白细胞介体。然后,通过使用酶联免疫吸附法分析选定细胞因子的表达情况,研究了不同剂量的三种纯SpA与恩布雷相比的效果。结果表明,与其他全长制剂和商业药物恩布雷相比,截短型重组 SpA 能更有效地减少细胞因子的表达。硅学分析表明,在截短蛋白中,随着回转半径的增加,IgG结合域的结构变得更加开放,更容易暴露于IgG。总之,我们的研究结果表明,蛋白 A 的截短形式是最有效的 SpA 形式,因为它能显著降低体外 PBMC 分泌的评估细胞因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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