Silica dioxide nanoparticles aggravate airway inflammation in an asthmatic mouse model via NLRP3 inflammasome activation

Regul Toxicol Pharmacol. 2020 Apr:112:104618. doi: 10.1016/j.yrtph.2020.104618. Epub 2020 Feb 19.

Abstract

Silica dioxide nanoparticles (SiONPs) are mainly used in the rubber industry; however, they are a major air pollutant in Asia. Thus, extensive research on this issue is required. In this study, we investigated the effects of SiONPs on asthma aggravation and elucidated the underlying mechanism using ovalbumin (OVA)-induced asthmatic mice model and in NCI-H292 cells. Mice exposed to SiONPs showed markedly increased Penh values, inflammatory cell counts, and inflammatory cytokine levels compared to OVA-induced asthmatic mice. Exposure to SiONPs also induced additional airway inflammation and mucus secretion with increases in protein expression levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, and interleukin (IL)-1β compared to those in OVA-induced asthmatic mice. Treatment of SiONPs in NCI-H292 cells also significantly increased mRNA expression levels of inflammatory cytokines accompanied with elevation in the levels of TXNIP, NLRP3 inflammasome, and IL-1β proteins in a concentration-dependent manner. Taken together, exposure to SiONPs aggravated asthma development, which is closely related to inflammasome activation. Our results provide useful information about the toxicological effects of SiONPs on asthma exacerbation and suggest the need to avoid SiONP exposure especially in individuals with respiratory diseases.

Keywords: Asthma; IL-1β; Inflammation; NLRP3 inflammasome; Silica nanoparticle; TXNIP.

MeSH terms

  • Animals
  • Asthma / metabolism*
  • Asthma / pathology
  • Cell Line, Tumor
  • Disease Models, Animal*
  • Female
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Nanoparticles / chemistry*
  • Respiratory System / metabolism
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / metabolism*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Silicon Dioxide