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

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.

• Authors: Xiang-Zhi Fang, Ya-Li Ge, Zhao-Yuan Chen, Hua-Qing Shu, Yi-Yi Yang, Yuan Yu, Xiao-Jing Zhou, Lin Chen, Shu-Nan Cui, Ya-Xin Wang, Shang-Long Yao, You Shang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 81 Pg. 106257 (Apr 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32044659 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Anti-Inflammatory Agents
• Carrier Proteins
• Heterocyclic Compounds, 4 or More Rings
• Lipopolysaccharides
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• NecroX-5
• Sulfones
• Txnip protein, mouse
• Thioredoxins
• Peroxidase

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Carrier Proteins (genetics, metabolism)
• Disease Models, Animal
• Gene Expression Regulation
• Heterocyclic Compounds, 4 or More Rings (therapeutic use)
• Humans
• Lipopolysaccharides (immunology)
• Lung (metabolism, pathology)
• Male
• Mice
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Peroxidase (metabolism)
• RAW 264.7 Cells
• Respiratory Distress Syndrome (drug therapy, immunology)
• Signal Transduction
• Sulfones (therapeutic use)
• Thioredoxins (genetics, metabolism)