Dexamethasone alleviate allergic airway inflammation in mice by inhibiting the activation of NLRP3 inflammasome

Int Immunopharmacol. 2020 Jan:78:106017. doi: 10.1016/j.intimp.2019.106017. Epub 2019 Nov 25.

Abstract

Dexamethasone (DEX) is the mainstay treatment for asthma, which is a common chronic airway inflammation disease. However, the mechanism of DEX resolute symptoms of asthma is not completely clear. Here, we aimed to analyze the effect of DEX on airway inflammation in OVA-induced mice and whether this effect is related to the inhibition of the activation of NLRP3 inflammasome. Female (C57BL/6) mice were used to establish the allergic airway inflammation model by inhalation OVA. The number of inflammatory cells in the bronchi alveolar lavage fluid (BALF) was counted by Swiss-Giemsa staining, and the contents of IL-1β, IL-18, IL-5 and IL-17 were detected by ELISA. The degree of inflammatory cells infiltration and mucous cells proliferation in lung tissue were separately observed by H&E and PAS staining. The proteins expression of NLRP3, pro-caspase-1, caspase-1, IL-1β, IL-6 and IL-17 in lung tissue were detected by Western blotting. We found that DEX significantly inhibited OVA-induced inflammatory cells infiltration, airway mucus secretion and goblet cell proliferation in mice. The total and classified numbers of inflammatory cells and the levels of IL-1β, IL-18, IL-5 and IL-17 in the BALF of the experimental group were significantly lower than those of the model group after DEX treatment. DEX also significantly inhibited the activity of NLRP3 inflammasome and reduced the protein contents of Pro-Caspase-1, Caspase-1, Capase-1/Pro-Caspase-1, IL-1β, IL-6 and IL-17 in lung tissues. Our study suggested that DEX alleviates allergic airway inflammation by inhibiting the activity of NLRP3 inflammasome and the levels of IL-1β and IL-18.

Keywords: Asthma; Dexamethasone; Inflammation; NLRP3 inflammasome.

MeSH terms

  • Animals
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / pathology
  • Dexamethasone / pharmacology*
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Female
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Humans
  • Inflammasomes / drug effects*
  • Inflammasomes / immunology
  • Inflammasomes / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology

Substances

  • Glucocorticoids
  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Dexamethasone
  • Ovalbumin