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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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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. |
format | Online Article Text |
id | pubmed-6556267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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