Proteinase activated receptor-2 and autophagy regulation: implications for premature lung ageing?

Kirsty McCallum*, Lynette Dunning (Contributor), Anne Crilly (Contributor), Marija Stankovic (Contributor), Mariarca Bailo (Contributor), John C. Lockhart (Contributor), Gary J. Litherland

*Corresponding author for this work

Research output: Contribution to conferencePoster

Abstract

Chronic Obstructive Pulmonary Disease (COPD) lungs display hallmarks of premature ageing. Autophagy is the catabolic process that eukaryotic cells utilise to degrade and recycle cellular components, increasing longevity and delaying the ageing process. COPD patients exhibit reduced lung autophagy, contributing to cellular senescence, although the underlying mechanisms are unclear. Proteinase activated receptor-2 (PAR2) is an important drug target for inflammatory conditions, which has documented roles in lung pathology. However, a role for PAR2 in lung ageing is hitherto unexplored.
Methods: Human epithelial cells (A549 and BEAS-2B lines, primary) were cultured prior to stimulation using PAR2 agonists (SLIGKV, trypsin) and autophagy quantified using a fluorescent marker of autophagosomes (CYTO-ID detection kit). Western blotting to analyse expression of ATGs (autophagy related genes) was used to confirm findings. PAR2 cellular expression was assessed by immunofluorescence.
PAR2 expression was demonstrated in human airway epithelial cells. Autophagic vesicles were successfully detected, and fluorescence levels detected modulated by appropriate autophagy controls. Stimulation of PAR2 activity, assessed alone and in combination with inflammatory stimuli, also caused modulation of the level of autophagic activity within airway epithelial cultures.
Our data indicate PAR2 as a potential regulator of autophagy in lung airway epithelia, suggesting a possible novel role in conditions such as COPD that feature premature lung ageing.


Original languageEnglish
Publication statusPublished - 5 Sep 2018
EventBritish Association for Lung Research Summer Meeting 2018: Inflammation in the Ageing Lung - University of Birmingham, Birmingham , United Kingdom
Duration: 5 Sep 20187 Sep 2018
https://www.balr.co.uk/meetings
https://www.balr.co.uk/meetings

Conference

ConferenceBritish Association for Lung Research Summer Meeting 2018
Abbreviated titleBALR
CountryUnited Kingdom
CityBirmingham
Period5/09/187/09/18
Internet address

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Keywords

  • Key Words - Ageing, Autophagy, PAR2, COPD, ATGs, Pulmonary, Epithelial

Cite this

McCallum, K., Dunning , L., Crilly, A., Stankovic, M., Bailo, M., Lockhart , J. C., & Litherland, G. J. (2018). Proteinase activated receptor-2 and autophagy regulation: implications for premature lung ageing?. Poster session presented at British Association for Lung Research Summer Meeting 2018, Birmingham , United Kingdom.