Autophagy inhibitors suppress environmental particulate matter-induced airway inflammation

Toxicol Lett. 2017 Oct 5:280:206-212. doi: 10.1016/j.toxlet.2017.08.081. Epub 2017 Sep 1.

Abstract

Particulate matter (PM) is a significant risk factor for airway injury. We have recently demonstrated a pivotal role of autophagy in mediating PM-induced airway injury. In the present study, we examined the possible effects of autophagy inhibitors spautin-1 and 3-Methyladenine (3-MA) in protection of PM-induced inflammatory responses. We observed that PM triggered autophagy in human bronchial epithelial (HBE) cells and in mouse airways. Spautin-1 or 3-MA inhibited PM-induced expression of inflammatory cytokines in HBE cells, and decreased the neutrophil influx and proinflammatory cytokines induced by PM in vivo. We further illustrated that autophagy inhibitors suppressed the inflammation responses via inhibition of the nuclear factor-кB (NF-кB) pathway. Thus, this study shows a paradigm that autophagy inhibitors effectively decrease the PM-induced airway inflammation via suppressing the NF-кB pathway, which may provide novel preventive and/or protective approaches for PM-related airway injury.

Keywords: Airway injury; Autophagy inhibitors; Particulate matter.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / pharmacology
  • Animals
  • Autophagy / drug effects*
  • Benzylamines / pharmacology*
  • Cell Line
  • Cytokines / genetics
  • Cytokines / metabolism
  • Environmental Pollutants / toxicity*
  • Gene Expression Regulation / physiology
  • Humans
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Particulate Matter / toxicity*
  • Quinazolines / pharmacology*

Substances

  • Benzylamines
  • Cytokines
  • Environmental Pollutants
  • Particulate Matter
  • Quinazolines
  • spautin-1
  • 3-methyladenine
  • Adenine