Protease activated receptor 2 (PAR2) antagonism reduces pro-inflammatory cytokine production in bronchial epithelial cells

Mariarca Bailo*, L. Dunning, J. Brzeszczynska, K. McIntosh, R. Plevin, S. L. Martin, G. P. Sergeant, C. S. Goodyear, G. S. Litherland, J. C. Lockhart, A. Crilly

*Corresponding author for this work

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

PAR2 is a G-protein coupled receptor which modulates inflammation via pro-inflammatory cytokine release. Chronic obstructive pulmonary disease (COPD) is associated with an abnormal inflammatory response by the lungs (Barnes, P. J. The Journal of allergy and clinical immunology 2016; 138: 16-27). The aim of this study was to investigate a putative role for PAR2 in COPD. Expression of PAR2 was evaluated in primary human bronchial epithelial cells derived from healthy controls and COPD patients (HBECs & DHBECs respectively) and bronchial epithelial cell lines (BEAS-2B) by immunofluorescence. Levels of secreted IL-6 and IL-8 were determined by ELISA. The role of PAR2 in BEAS-2B was investigated using the PAR2 agonist 2-Furoyl-LIGRLO-amide (10 μM) and the antagonist AZ8838 (Cheng R. et al. Nature 2017; 545: 112-115). Immunofluorescent microscopy showed PAR2 expression in HBECs, COPD HBECs and BEAS-2B. Evaluation of spontaneous cytokine secretion revealed that both IL-6 and IL-8 were significantly increased (p<0.01) in DHBECs compared to HBECs and BEAS-2B. Inhibition of PAR2 activation in BEAS-2B by AZ8838 significantly reduced IL-8 (24 h) and IL-6 (48 h) secretion (figure below). Using a recently described antagonist (AZ8838), this study demonstrates a role for PAR2 in pro-inflammatory cytokine release in bronchial epithelial cells, suggesting PAR2 may contribute to the pathogenesis of COPD.
Original languageEnglish
Article number2292
JournalEuropean Respiratory Journal
Volume56
Issue numberSupplement 64
DOIs
Publication statusPublished - 28 Oct 2020

Fingerprint

Dive into the research topics of 'Protease activated receptor 2 (PAR2) antagonism reduces pro-inflammatory cytokine production in bronchial epithelial cells'. Together they form a unique fingerprint.

Cite this