Reactive oxygen species are involved in eosinophil extracellular traps release and in airway inflammation in asthma

J Cell Physiol. 2019 Dec;234(12):23633-23646. doi: 10.1002/jcp.28931. Epub 2019 Jun 10.

Abstract

In asthma, there are high levels of inflammatory mediators, reactive oxygen species (ROS), and eosinophil extracellular traps (EETs) formation in airway. Here, we attempted to investigate the ROS involvement in EETs release and airway inflammation in OVA-challenged mice. Before the intranasal challenge with ovalbumin (OVA), animals were treated with two ROS inhibitors, N-acetylcysteine (NAC) or diphenyleneiodonium (DPI). We showed that NAC treatment reduced inflammatory cells in lung. DPI and NAC treatments reduced eosinophil peroxidase (EPO), goblet cells hyperplasia, proinflammatory cytokines, NFκB p65 immunocontent, and oxidative stress in lung. However, only the NAC treatment improved mitochondrial energy metabolism. Moreover, the treatments with DPI and NAC reduced EETs release in airway. This is the first study to show that ROS are needed for EETs formation in asthma. Based on our results, NAC and DPI treatments can be an interesting alternative for reducing airway inflammation, mitochondrial damage, and EETs release in asthma.

Keywords: DNA extracellular traps; N-acetylcysteine; diphenyleneiodonium; experimental asthma; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Asthma / pathology*
  • Cytokines / metabolism
  • Energy Metabolism / physiology
  • Eosinophil Peroxidase / metabolism
  • Eosinophils / metabolism*
  • Extracellular Traps / metabolism*
  • Female
  • Goblet Cells / pathology
  • Lung / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria / metabolism
  • Onium Compounds / pharmacology
  • Ovalbumin / toxicity
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism*
  • Transcription Factor RelA / metabolism

Substances

  • Cytokines
  • Onium Compounds
  • Reactive Oxygen Species
  • Rela protein, rat
  • Transcription Factor RelA
  • diphenyleneiodonium
  • Ovalbumin
  • Eosinophil Peroxidase
  • Acetylcysteine