Celastrol alleviates murine lupus nephritis via inducting CD4+Foxp3+ regulatory T cells.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2022-01-01 Epub Date: 2022-07-06 DOI:10.5603/FHC.a2022.0020

Guangbo Xiang, Kai Shi, Jinjun Wang

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引用次数: 5

Abstract

Introduction: Lupus nephritis (LN) is an autoimmune glomerulonephritis secondary to systemic lupus erythematosus. Commonly, immunosuppressive agents are required for treating LN. However, frequent use of conventional immunosuppressants may produce a variety of side effects. Hence, seeking alternative drugs for treating LN is very important. This report aims to figure out the immunoregulatory efficacy of celastrol (CLT) in LN.

Material and methods: A spontaneous in vivo model of LN was established in FasL-deficient B6/gld mice. ELISA was used for analyzing serum creatinine (Scr) and anti-dsDNA levels in mice. IHC staining, immunofluorescence and hematoxylin-eosin and PAS staining were applied to determine renal immunopathology and histology. Cytokine gene levels were assessed using RT qPCR. CD4+Foxp3+ Treg frequency in murine kidneys, lymph nodes and spleens was determined using flow cytometry analysis.

Results: CLT treatment alleviated renal dysfunction and renal injury in LN-prone B6/gld mice. Moreover, CLT reduced CD3+ T cell infiltration and inhibited proinflammatory cytokine expression in renal tissues of B6/gld mice. Importantly, CLT enhanced CD4+FoxP3+ Treg frequency in kidneys, lymph nodes and spleens of B6/gld mice.

Conclusions: CLT exerts therapeutic effects on murine LN by improving renal function and immunopathology and inducing CD4+FoxP3+ Tregs.

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Celastrol通过诱导CD4+Foxp3+调节性T细胞减轻小鼠狼疮性肾炎。

狼疮肾炎(LN)是一种继发于系统性红斑狼疮的自身免疫性肾小球肾炎。通常，治疗LN需要免疫抑制剂。然而，经常使用常规免疫抑制剂可能会产生各种副作用。因此，寻找治疗LN的替代药物是非常重要的。本报告旨在了解celastrol (CLT)在LN中的免疫调节作用。材料与方法:建立fasl缺失B6/ gold小鼠体内自发LN模型。ELISA法测定小鼠血清肌酐(Scr)和抗dsdna水平。采用免疫组化染色、免疫荧光染色、苏木精-伊红染色和PAS染色检测肾脏免疫病理组织学。采用RT - qPCR检测细胞因子基因水平。流式细胞术检测小鼠肾脏、淋巴结和脾脏中CD4+Foxp3+ Treg频率。结果:CLT治疗可减轻ln易感B6/ gold小鼠的肾功能障碍和肾损伤。此外，CLT减少了B6/ gold小鼠肾组织中CD3+ T细胞的浸润，抑制了促炎细胞因子的表达。重要的是，CLT提高了B6/ gold小鼠肾脏、淋巴结和脾脏中CD4+FoxP3+ Treg的频率。结论:CLT通过改善小鼠肾功能和免疫病理，诱导CD4+FoxP3+ Tregs来治疗LN。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.

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