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


ABSTRACT: 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 (ROR?t) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of ROR?t activity by 3?-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 ROR?t activity and prevent SLE pathogenesis in a pristane-induced LN model. The results showed that AOA decreased ROR?t 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.

SUBMITTER: Zhou X 

PROVIDER: S-EPMC6556267 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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3<i>β</i>-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation.

Zhou Xiaoqing X   Chen Huanpeng H   Wei Fengjiao F   Zhao Qingyu Q   Su Qiao Q   Liang Jinhao J   Yin Meng M   Tian Xuyan X   Liu Zhonghua Z   Yu Bolan B   Bai Chuan C   He Xixin X   Huang Zhaofeng Z  

Journal of immunology research 20190522


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 (ROR<i>γ</i>t) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of ROR<i>γ</i>t activity by 3<i>β</i>-acetyloxy-oleanolic acid (AOA), a small molecule isolated from the root of <i>Symplocos laurina</i>, a traditional he  ...[more]

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2020-02-19 | GSE140104 | GEO