Proteinase activated receptor-2 and autophagy regulation in airway epithelia cells

Kirsty McCallum, Mariarca Bailo, Lynette Dunning, Marija Stankovic, Lorcan McGarvey, Mark Hollywood, Carl S. Goodyear, Anne Crilly, John C. Lockhart, Gary J. Litherland

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Lungs from patients with chronic obstructive pulmonary disease (COPD) display hallmarks of premature ageing including reduced autophagy, which contributes to cellular senescence. However, mechanisms underlying dysregulated lung autophagy remain unclear. While proteinase activated receptor-2 (PAR2) is a drug target for inflammatory conditions, with documented roles in lung pathology, a role for this receptor in lung ageing is yet unexplored.

To investigate this, primary human epithelial cells and epithelial cell lines were stimulated with PAR2 activators (SLIGKV, trypsin) and autophagy quantified using a fluorescent marker of autophagosomes (CYTO-ID detection kit). Western blotting to analyse expression of autophagyrelated proteins was used to confirm findings. PAR2 expression was assessed by immunofluorescence.

We confirmed that PAR2 was on human airway epithelial cells. Autophagic vesicles were successfully detected and modulated by appropriate autophagy control stimuli. Stimulation of PAR2, assessed alone and in combination with inflammatory stimuli, resulted in modulation of the level of autophagic activity within airway epithelial cultures.

Our study provides the first data that suggests a role for PAR2 in the regulation of autophagy in lung airway epithelia. This further suggests a possible novel targetable mechanism underlying conditions such as COPD that feature premature lung ageing
Original languageEnglish
Pages (from-to)S272-S273
Number of pages2
JournalIrish Journal of Medical Science
Volume187
Issue numberSupplement 8
DOIs
Publication statusPublished - 8 Oct 2018
EventIrish Thoracic Society Annual Scientific Meeting - Hastings Europa Hotel, Belfast, United Kingdom
Duration: 23 Nov 201824 Nov 2018

Keywords

  • COPD
  • BREATH
  • interreg va
  • SEUPB
  • PAR2
  • Autophagy
  • airway epithelial cells

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