2. Academic Validation
  3. NecroX-5 alleviate lipopolysaccharide-induced acute respiratory distress syndrome by inhibiting TXNIP/NLRP3 and NF-κB

NecroX-5 alleviate lipopolysaccharide-induced acute respiratory distress syndrome by inhibiting TXNIP/NLRP3 and NF-κB

  • Int Immunopharmacol. 2020 Apr;81:106257. doi: 10.1016/j.intimp.2020.106257.
Xiang-Zhi Fang 1,  Ya-Li Ge 2,  Zhao-Yuan Chen 3,  Hua-Qing Shu 3,  Yi-Yi Yang 4,  Yuan Yu 3,  Xiao-Jing Zhou 3,  Lin Chen 3,  Shu-Nan Cui 3,  Ya-Xin Wang 3,  Shang-Long Yao 5,  You Shang 6
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan, Hubei 430022, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, Hubei 430022, China; Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
  • 2 Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
  • 3 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan, Hubei 430022, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
  • 4 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong Universityof Science and Technology, Wuhan, Hubei 430022, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
  • 5 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong Universityof Science and Technology, Wuhan, Hubei 430022, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. Electronic address: ysltian@163.com.
  • 6 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, HuazhongUniversity of Science and Technology, Wuhan, Hubei 430022, China; Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, Hubei 430022, China. Electronic address: you_shang@yahoo.com.
PMID: 32044659 DOI: 10.1016/j.intimp.2020.106257
Abstract

The activation of NLRP3 inflammasome and NF-κB pathway, associating with oxidativestress, have been implicated in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). NecroX-5 has been reported to exhibit theeffectsofanti-oxidation and anti-stress in various diseases. However, the role of NecroX-5 in ALI has not been explicitly demonstrated. The aim of this study was to explore the therapeutic effects and potential mechanism action of NecroX-5 on ALI. Here, we found that NecroX-5 pretreatment dramatically diminished the levels of IL-1β, IL-18 and ROS in in RAW264.7 cells challenged with LPS and ATP. Furthermore, NecroX-5 suppressed the activation of NLRP3 inflammasome and NF-κB signalpathway. In addition, NecroX-5 also inhibited the thioredoxin-interacting protein (TXNIP) expression. In vivo, NecroX-5 reduced the LPS-induced lung histopathological injury, the number of TUNEL-positive cells, lung wet/dry (W/D) ratio, levels of total protein and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) in mice. Additionally, LPS-induced upregulation of myeloperoxidase (MPO), ROS production and malondialdehyde (MDA) were inhibited by NecroX-5 administration. Thus, our results demonstrate that NecroX-5 protects against LPS-induced ALI by inhibiting TXNIP/NLRP3 and NF-κB.

Keywords

Acute lung injury; Inflammation; Intervention; NLRP3; NecroX-5.

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