Influence of bacterial lectin on key regulatory links of functional activity of macrophages in mice with Ehrlich carcinoma.

A V Chumak, N I Fedosova, V M Shcherbina, N L Cheremshenko, О М Karaman, V F Chekhun
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Abstract

Background: Recent studies have shown the potential of using different approaches for immunotherapy in cancer treatment. Macrophages (Mph) are one of the promising targets for immunotherapy.

Aim: To investigate changes in the functional activity of Mph in mice with Ehrlich carcinoma by nitric oxide (NO)/arginase (Arg), IRF4/IRF5 and STAT1/STAT6 ratios caused by administration of lectin from B. subtilis IMV-7724.

Materials and methods: From the 2nd day after Ehrlich carcinoma inoculation into female Balb/c mice, lectin from B. subtilis IMV B-7724 (0.02 mg/mouse) was administered for 10 days. The peritoneal Mph were isolated on days 14, 21, and 28 after tumor transplantation and their functional state (NO production, Arg activity and cytotoxic activity) was examined. The levels of mRNA expression of transcription factors STAT-1, STAT-6, IRF5, IRF4 were evaluated.

Results: In lectin-treated animals with Ehrlich carcinoma, the functional state of Mph (NO/Arg ratio, index of cytotoxic activity) was maintained at the level of intact mice exceeding the values in untreated animals with Ehrlich carcinoma at late terms of tumor growth (21, 28 days). Analysis of mRNA expression levels of transcription factors in these animals showed a significant increase (p < 0.05) in the ratio of STAT1/STAT6 on the day 21 and IRF5/IRF4 on day 28 of tumor growth compared to that in untreated mice.

Conclusions: Administration of lectin from B. subtilis IMV B-7724 to mice with Ehrlich carcinoma led to the prevalence of Mph exhibiting the functional properties of M1 type at late-term tumor growth. The transcription factors of the STAT and IRF signaling pathways are involved in the process of Mph polarization induced by lectin from B. subtilis IMV B-7724.

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细菌凝集素对埃利希癌小鼠巨噬细胞功能活性关键调控环节的影响。
背景:最近的研究表明,在癌症治疗中使用不同的免疫治疗方法具有潜力。巨噬细胞(Mph)是免疫治疗的一个很有前途的靶点。目的:探讨枯草芽孢杆菌IMV-7724凝集素引起的一氧化氮(NO)/精氨酸酶(Arg)、IRF4/IRF5和STAT1/STAT6比值对埃利希癌小鼠心肌功能活性的影响。材料与方法:雌性Balb/c小鼠接种埃利希癌后第2天起,给予枯草芽孢杆菌IMV B-7724凝集素(0.02 mg/只)10 d。分别于肿瘤移植后第14、21、28天分离腹腔Mph细胞,检测其功能状态(NO生成、Arg活性和细胞毒活性)。评估转录因子STAT-1、STAT-6、IRF5、IRF4的mRNA表达水平。结果:凝集素处理的埃利希癌动物,在肿瘤生长后期(21、28天),其细胞毒活性指数(NO/Arg比值)的功能状态维持在完整小鼠的水平,超过未处理的埃利希癌动物。转录因子mRNA表达水平分析显示,与未处理小鼠相比,肿瘤生长第21天STAT1/STAT6和第28天IRF5/IRF4的比值显著升高(p < 0.05)。结论:枯草芽孢杆菌IMV B-7724凝集素对埃利希癌小鼠的作用导致肿瘤生长后期Mph的流行,并表现出M1型的功能特征。枯草芽孢杆菌IMV B-7724凝集素诱导Mph极化的过程中有STAT和IRF信号通路的转录因子参与。
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来源期刊
Experimental oncology
Experimental oncology Medicine-Oncology
CiteScore
1.40
自引率
0.00%
发文量
49
期刊介绍: The Experimental Oncology is an English-language journal that publishes review articles, original contributions, short communications, case reports and technical advances presenting new data in the field of experimental and fundamental oncology. Manuscripts should be written in English, contain original work, which has not been published or submitted for publication elsewhere. It also implies the transfer of the Copyright from the author to “Experimental Oncology”. No part of journal publications may be reproduced, stored in a retrieval system or transmitted in any form or by any means without the prior permission of the publisher.
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