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Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis

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Abstract

Objectives

This study evaluated the anti-inflammatory effect of niclosamide in tumor necrosis factor (TNF)-α-stimulated human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and inhibitory effects on migration and invasion in RA FLS and investigated the signal mechanism, and further explored the treatment activity of niclosamide on collagen-induced arthritis (CIA).

Methods

The levels of interleukin (IL)-1β, IL-6, IL-8, IL-10,IL-17A and interferon (IFN)-γ in cultural supernatants were measured by multiplex cytokine assay kits. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction proteins expression was measured by western blot. The in vivo suppressive effects of niclosamide were elucidated on CIA in a mouse model.

Results

Niclosamide reduced the secretion of IL-1β, IL-6, IL-8, IL-17A and IFN-γ from TNF-α-induced RA FLS in a dose-dependent manner. Niclosamide inhibits FBS-induced migration and invasion and exhibits F-actin alterations in RA FLS. Niclosamide decreased the phosphorylation of c-Jun N-terminal kinase and ERK in TNF-α-stimulated RA FLS and blocked TNF-α-induced IKK, IκBα phosphorylation and translocation of p65. Niclosamide treatments reduced the severity of CIA model.

Conclusions

Our data suggest for the first time that niclosamide posses the anti-inflammatory effect in RA both in vitro and in vivo.

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Acknowledgments

The authors would like to thank Jinjin Fan for her technical assistance. This work is supported by grants from National Natural Science Foundation of China (Grant no. 81373182 and U1401222), China Ministry of Education Foundation (Grant no. 20100171110058), Guangdong Natural Science Foundation (Grant no. 2011020002358), Guangdong Project of Science and Technology (Grant no. 2011B080701011 and 2008B030301064).

Conflict of interest

The authors have declared no conflicts of interest.

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    Authors and Affiliations

    1. Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People’s Republic of China

      Liuqin Liang, Mingcheng Huang, Youjun Xiao, Shan Zen, Minxu Lao, Yaoyao Zou, Maohua Shi, Xiuyan Yang & Hanshi Xu

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    1. Liuqin Liang
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    Correspondence to Hanshi Xu.

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    Responsible Editor: John Di Battista.

    Liuqin Liang and Mingcheng Huang have contributed equally to this study.

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    Liang, L., Huang, M., Xiao, Y. et al. Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis. Inflamm. Res. 64, 225–233 (2015). https://doi.org/10.1007/s00011-015-0801-5

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    • DOI: https://doi.org/10.1007/s00011-015-0801-5

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