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Inflammation

pp 1–14 | Cite as

Tizoxanide Inhibits Inflammation in LPS-Activated RAW264.7 Macrophages via the Suppression of NF-κB and MAPK Activation

  • Jiaoqin Shou
  • Xiangzhen Kong
  • Xiaoyang Wang
  • Ying Tang
  • Chunmei Wang
  • Mi Wang
  • Lifang Zhang
  • Yingchun Liu
  • Chenzhong Fei
  • Feiqun Xue
  • Juan Li
  • Keyu ZhangEmail author
ORIGINAL ARTICLE
  • 125 Downloads

Abstract

Tizoxanide is the main active metabolite of nitazoxanide. Nitazoxanide and tizoxanide have a broad-spectrum anti-infective effect, including parasites, bacteria, and virus. In the present study, we investigated the anti-inflammatory effect of tizoxanide on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and revealed underlying molecular mechanisms. The results showed that tizoxanide significantly suppressed production of NO as well as pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α in dose-dependent manner. Meanwhile, the levels of gene expression of these cytokines were inhibited significantly by tizoxanide that was discovered using RT-PCR. The increased protein levels of inducible nitric oxide synthase, heme oxygenase-1, and cyclooxygenase-2 by LPS in the cells were also reduced by tizoxanide. Moreover, we found that tizoxanide inhibited the phosphorylation of IKK-α and degradation of IκB by LPS in macrophage cells. The increased protein levels of p65 induced by LPS in the cytoplasm and nucleus were both decreased by tizoxanide, and the nuclear translocation of p65 was also restrained in cell imaging. In addition, tizoxanide considerably also inhibited LPS-activated JNK, p38, and ERK phosphorylation in RAW264.7 cells. Taken together, our results suggested that tizoxanide exerts anti-inflammatory effects, by inhibiting the production of pro-inflammatory cytokines and suppressing of the activation of the NF-κB and the MAPK signaling pathways in LPS-treated macrophage cells.

KEY WORDS

tizoxanide RAW264.7 cells lipopolysaccharide anti-inflammation NF-κB MAPKs 

Notes

Funding Information

This work is financially supported by the National Key Technology Research and Development Program of China (2015BAD11B00). This project is also supported in part by the National Natural Science Foundation of China (31872516) and the National Key Research and Development Program of China (2018YFD0500302).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jiaoqin Shou
    • 1
    • 2
  • Xiangzhen Kong
    • 1
  • Xiaoyang Wang
    • 1
  • Ying Tang
    • 1
  • Chunmei Wang
    • 1
  • Mi Wang
    • 1
  • Lifang Zhang
    • 1
  • Yingchun Liu
    • 1
  • Chenzhong Fei
    • 1
  • Feiqun Xue
    • 1
  • Juan Li
    • 2
  • Keyu Zhang
    • 1
    Email author
  1. 1.Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research InstituteChinese Academy of Agricultural SciencesShanghaiChina
  2. 2.College of ChemistryXiangtan UniversityXiangtanChina

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