A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury

  • FASEB J. 2017 Feb;31(2):711-718. doi: 10.1096/fj.201600840R.
Xiaomeng Ren  1 ,  Xinzhi Li  1 ,  Linna Jia  1 ,  Deheng Chen  2 ,  Hai Hou  3 ,  Liangyou Rui  4 ,  Yujun Zhao  5 ,  Zheng Chen  6
Affiliations
  • 1. Key Laboratory of Molecular Epigenetics of the Ministry of Education, School of Life Sciences, Northeast Normal University, Changchun, China.
  • 2. State Key Laboratory of Drug Research, Shanghai Institute of Meteria Medica, Chinese Academy of Sciences, Shanghai, China.
  • 3. Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China; and.
  • 4. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • 5. State Key Laboratory of Drug Research, Shanghai Institute of Meteria Medica, Chinese Academy of Sciences, Shanghai, China; [email protected].
  • 6. Key Laboratory of Molecular Epigenetics of the Ministry of Education, School of Life Sciences, Northeast Normal University, Changchun, China; [email protected].
PMID: 27871061 DOI: 10.1096/fj.201600840R
Abstract

Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-κB-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown. In this study, a small-molecule inhibitor of NIK, B022, was found to be a potent and selective chemical probe for liver inflammation and injury. B022 inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing and inflammatory gene expression, both in vitro and in vivo Furthermore, in vivo administration of B022 protected against not only NIK but also CCl4-induced liver inflammation and injury. Our data suggest that inhibition of NIK is a novel strategy for treatment of liver inflammation, oxidative stress, and injury.-Ren, X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.

Keywords
CCl4; NIK; inflammation; liver injury.
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