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Berberine Ameliorates Pro-inflammatory Cytokine-Induced Endoplasmic Reticulum Stress in Human Intestinal Epithelial Cells In Vitro

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Abstract

Endoplasmic reticulum stress (ER stress) in intestinal epithelial cells (IECs) plays an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). The aim of this study is to explore the potential of berberine (BBR) in regulating pro-inflammatory cytokine-induced ER stress and apoptosis in IECs. ER stress in cultured Caco-2 cells was induced by IFN-γ/TNF-α and tunicamycin, respectively. The experimental groups were pretreated with BBR. Cell viability was determined by MTT assay. In vitro apoptosis was examined by flow cytometry using annexin V-FITC labeling. The molecular markers of ER stress, including GRP-78, p-JNK, caspase-12, and cleaved caspase-3 were analyzed by Western blot. Xbp-1 mRNA splicing was detected by RT-PCR. Pretreatment of BBR helped to survive in cytokine-induced Caco-2 cells. BBR significantly attenuated cytokine-induced Caco-2 apoptosis. GRP78 expression and xbp-1 mRNA splicing were enhanced significantly in the presence of IFN-γ/TNF-α and tunicamycin, and they could be dampened by BBR. Further study revealed BBR could downregulate JNK phosphorylation, and the level of caspase-12 and cleaved caspase-3. Berberine can ameliorate pro-inflammatory cytokines induced ER stress in vitro, and it might be one of the targeted therapeutic agents for IBD.

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Acknowledgments

This work was supported by National Natural Science Foundation in China (30901420, 30972880, and 30801086), and Scientific Research Fund in Jiangsu Province (BK2008328).

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Authors and Affiliations

  1. Department of General Surgery, Jinling Hospital, Second Military Medical University, Nanjing, China

    Xianhua Hao, Jianfeng Gong, Weiming Zhu, Ning Li & Jieshou Li

  2. School of Medicine, Nanjing University, Nanjing, China

    Anlong Yao, Jianfeng Gong, Weiming Zhu, Ning Li & Jieshou Li

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  1. Xianhua Hao
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  3. Jianfeng Gong
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Correspondence to Jianfeng Gong.

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Hao, X., Yao, A., Gong, J. et al. Berberine Ameliorates Pro-inflammatory Cytokine-Induced Endoplasmic Reticulum Stress in Human Intestinal Epithelial Cells In Vitro . Inflammation 35, 841–849 (2012). https://doi.org/10.1007/s10753-011-9385-6

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  • DOI: https://doi.org/10.1007/s10753-011-9385-6

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