Analyses of the toxic properties of recombinant human Cyclophilin A in mice

IF 2.4 4区医学 Q3 TOXICOLOGY

Journal of Immunotoxicology Pub Date : 2019-01-01 DOI:10.1080/1547691X.2019.1665597

A. Kalinina, Mariya Zamkova, E. Antoshina, L. Trukhanova, Tatyana Gorkova, D. Kazansky, L. Khromykh

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引用次数: 8

Abstract

Abstract Cyclophilin A (CypA), an 18 kDa multi-functional protein with cis–trans isomerase activity, is both a ligand for cyclosporine A and a proinflammatory factor. CypA is also a chemoattractant for hemopoietic stem cells and progenitors of different lineages, and can mediate regenerative processes in an organism. Accumulated experimental data have suggested there are practical applications for this protein in the treatment of several diseases (i.e. neutralization of cyclosporine A side effects, etc.). However, the range of CypA safe doses as well as its toxic effects remain unknown. The study here investigated the acute toxicity of a single intraperitoneal (IP) or subcutaneous (SC) dosing of recombinant human CypA (rhCypA) in both female and male mice and its effect on gene expression of acute phase proteins (APP) in the female mice after IP treatment. The results showed that toxicity of rhCypA was most evident in female and male mice dosed IP with 750 mg/kg, and manifested as kidney injury and increased granulocyte/lymphocyte ratios in the blood. Enhanced expression of Sаа1 and Sаа2 genes was induced with doses of 0.1–2 mg/mouse of rhCypA. Injection of the maximal dose (750 mg/kg) significantly stimulated expression of all the APP genes studied.

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重组人亲环蛋白A对小鼠的毒性分析

摘要亲环素A（CypA），一种18 具有顺反异构酶活性的kDa多功能蛋白，既是环孢菌素a的配体，也是促炎因子。CypA也是不同谱系的造血干细胞和祖细胞的化学引诱剂，可以介导生物体的再生过程。积累的实验数据表明，这种蛋白质在治疗几种疾病（如环孢素A副作用的中和等）方面有实际应用。然而，CypA的安全剂量范围及其毒性作用仍然未知。本文研究了单次腹膜内（IP）或皮下（SC）给药重组人CypA（rhCypA）对雌性和雄性小鼠的急性毒性及其对IP治疗后雌性小鼠急性期蛋白（APP）基因表达的影响。结果表明，rhCypA的毒性在雌性和雄性小鼠中最为明显 mg/kg，表现为肾损伤和血液中粒细胞/淋巴细胞比率增加。0.1–2剂量可诱导Sаа1和Sа2基因表达增强 mg/小鼠rhCypA。注射最大剂量（750 mg/kg）显著刺激所研究的所有APP基因的表达。

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

Journal of Immunotoxicology 医学-毒理学

CiteScore

6.70

自引率

3.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Immunotoxicology is an open access, peer-reviewed journal that provides a needed singular forum for the international community of immunotoxicologists, immunologists, and toxicologists working in academia, government, consulting, and industry to both publish their original research and be made aware of the research findings of their colleagues in a timely manner. Research from many subdisciplines are presented in the journal, including the areas of molecular, developmental, pulmonary, regulatory, nutritional, mechanistic, wildlife, and environmental immunotoxicology, immunology, and toxicology. Original research articles as well as timely comprehensive reviews are published.