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3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation

Th17 activity has been implicated in systemic lupus erythematosus (SLE), which is a systemic autoimmune disease with a typical clinical manifestation of lupus nephritis (LN). Retinoic acid receptor-related orphan receptor gamma t (RORγt) has been shown to be important for Th17 differentiation. In th...

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Autores principales: Zhou, Xiaoqing, Chen, Huanpeng, Wei, Fengjiao, Zhao, Qingyu, Su, Qiao, Liang, Jinhao, Yin, Meng, Tian, Xuyan, Liu, Zhonghua, Yu, Bolan, Bai, Chuan, He, Xixin, Huang, Zhaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556267/
https://www.ncbi.nlm.nih.gov/pubmed/31240232
http://dx.doi.org/10.1155/2019/2431617
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author Zhou, Xiaoqing
Chen, Huanpeng
Wei, Fengjiao
Zhao, Qingyu
Su, Qiao
Liang, Jinhao
Yin, Meng
Tian, Xuyan
Liu, Zhonghua
Yu, Bolan
Bai, Chuan
He, Xixin
Huang, Zhaofeng
author_facet Zhou, Xiaoqing
Chen, Huanpeng
Wei, Fengjiao
Zhao, Qingyu
Su, Qiao
Liang, Jinhao
Yin, Meng
Tian, Xuyan
Liu, Zhonghua
Yu, Bolan
Bai, Chuan
He, Xixin
Huang, Zhaofeng
author_sort Zhou, Xiaoqing
collection PubMed
description Th17 activity has been implicated in systemic lupus erythematosus (SLE), which is a systemic autoimmune disease with a typical clinical manifestation of lupus nephritis (LN). Retinoic acid receptor-related orphan receptor gamma t (RORγt) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of RORγt activity by 3β-acetyloxy-oleanolic acid (AOA), a small molecule isolated from the root of Symplocos laurina, a traditional herb belonging to South China. We demonstrated that AOA can inhibit RORγt activity and prevent SLE pathogenesis in a pristane-induced LN model. The results showed that AOA decreased RORγt transcription activity in a reporter assay and prevented Th17 differentiation in vitro. In vivo studies showed that AOA treatment decreased serum anti-dsDNA antibody and alleviated renal pathologic damage as well as antibody complex accumulation in the pristane-induced LN model. These results demonstrated that AOA can improve the clinical manifestation of LN, indicating potential application in SLE therapy.
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spelling pubmed-65562672019-06-25 3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation Zhou, Xiaoqing Chen, Huanpeng Wei, Fengjiao Zhao, Qingyu Su, Qiao Liang, Jinhao Yin, Meng Tian, Xuyan Liu, Zhonghua Yu, Bolan Bai, Chuan He, Xixin Huang, Zhaofeng J Immunol Res Research Article Th17 activity has been implicated in systemic lupus erythematosus (SLE), which is a systemic autoimmune disease with a typical clinical manifestation of lupus nephritis (LN). Retinoic acid receptor-related orphan receptor gamma t (RORγt) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of RORγt activity by 3β-acetyloxy-oleanolic acid (AOA), a small molecule isolated from the root of Symplocos laurina, a traditional herb belonging to South China. We demonstrated that AOA can inhibit RORγt activity and prevent SLE pathogenesis in a pristane-induced LN model. The results showed that AOA decreased RORγt transcription activity in a reporter assay and prevented Th17 differentiation in vitro. In vivo studies showed that AOA treatment decreased serum anti-dsDNA antibody and alleviated renal pathologic damage as well as antibody complex accumulation in the pristane-induced LN model. These results demonstrated that AOA can improve the clinical manifestation of LN, indicating potential application in SLE therapy. Hindawi 2019-05-22 /pmc/articles/PMC6556267/ /pubmed/31240232 http://dx.doi.org/10.1155/2019/2431617 Text en Copyright © 2019 Xiaoqing Zhou et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhou, Xiaoqing
Chen, Huanpeng
Wei, Fengjiao
Zhao, Qingyu
Su, Qiao
Liang, Jinhao
Yin, Meng
Tian, Xuyan
Liu, Zhonghua
Yu, Bolan
Bai, Chuan
He, Xixin
Huang, Zhaofeng
3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation
title 3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation
title_full 3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation
title_fullStr 3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation
title_full_unstemmed 3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation
title_short 3β-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation
title_sort 3β-acetyloxy-oleanolic acid attenuates pristane-induced lupus nephritis by regulating th17 differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556267/
https://www.ncbi.nlm.nih.gov/pubmed/31240232
http://dx.doi.org/10.1155/2019/2431617
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