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Effects of Arsenic Trioxide on INF-gamma Gene Expression in MRL/lpr Mice and Human Lupus

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Abstract

Arsenic trioxide (As2O3; ATO), a traditional Chinese medicine, is used to treat patients with acute promye-locytic leukemia, while its application for treatment of systemic lupus erythematosus (SLE) is still under evaluation. The high expression of INF-gamma (INF-γ) is a primary pathogenic factor in SLE. It is found that ATO can reduce INF-γ expression levels in lupus-prone mice, whereas it is not clear whether ATO has the same effect on SLE patients. Therefore, this study was to investigate the underlying mechanism of the effects of ATO on the expression of INF-γ in splenocytes of MRL/lpr mice and PBMCs of human lupus. The mRNA and protein expression levels of INF-γ were assessed by real-time RT-PCR and ELISA, respectively. The histone acetylation status of the INF-γ promoter and the binding of RNA polymerase II (RNA Pol II) to the INF-γ promoter were detected using a chromatin immunoprecipitation (ChIP) technique. The mRNA and protein expression levels of INF-γ decreased in both splenocytes of MRL/lpr mice and PBMCs of SLE patients with ATO treatment, which were accompanied by reduced histone H4 and H3 acetylation in INF-γ promoter and decreased combination of RNA Pol II to the INF-γ promoter. Therefore, ATO may reduce the expression level of the INF-γ by altering the levels of INF-γ promoter acetylation and the combination of RNA Pol II to the INF-γ promoter in splenocytes of MRL/lpr mice and PBMCs of SLE patients.

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Acknowledgements

We thank Prof. Kang Yu (Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University) for providing assistance with experimental techniques.

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Authors and Affiliations

  1. Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Hongye Hu

  2. Department of Pneumology, The People Hospital of Pingyang, Wenzhou, Zhejiang Province, China

    Enjiu Chen

  3. Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang Street, Ouhai District, Wenzhou, Zhejiang Province, 325000, China

    Yongji Li, Xiaochun Zhu, Ting Zhang & Xiaofang Zhu

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  1. Hongye Hu
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Correspondence to Xiaofang Zhu.

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This study was carried out with approval of the Ethics Committee of First Affiliated Hospital, Wenzhou Medical University.

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The authors declare that they have no competing interests.

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Hu, H., Chen, E., Li, Y. et al. Effects of Arsenic Trioxide on INF-gamma Gene Expression in MRL/lpr Mice and Human Lupus. Biol Trace Elem Res 184, 391–397 (2018). https://doi.org/10.1007/s12011-017-1206-9

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  • DOI: https://doi.org/10.1007/s12011-017-1206-9

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