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

Mariarca Bailo; Lynette Dunning; Joanna Brzeszczynska; Kathryn McIntosh; Robin Plevin; S.L. Martin; Gerard P Sergeant; Carl Goodyear; Gary Litherland; John Lockhart; Anne Crilly

doi:10.1183/13993003.congress-2020.2292

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.

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 language	English
Article number	2292
Journal	European Respiratory Journal
Volume	56
Issue number	Suppl. 64
DOIs	https://doi.org/10.1183/13993003.congress-2020.2292
Publication status	Published - 07 Sept 2020
Event	European Respiratory Society International Congress 2020 - virtual, online Duration: 07 Sept 2020 → 09 Sept 2020

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Bailo, M., Dunning, L., Brzeszczynska, J., McIntosh, K., Plevin, R., Martin, S. L., Sergeant, G. P., Goodyear, C., Litherland, G., Lockhart, J., & Crilly, A. (2020). Protease activated receptor 2 (PAR2) antagonism reduces pro-inflammatory cytokine production in bronchial epithelial cells. European Respiratory Journal, 56(Suppl. 64), Article 2292. https://doi.org/10.1183/13993003.congress-2020.2292

@article{4929b3e95e424d698aba3a2fc113f0f0,

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

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.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.",

author = "Mariarca Bailo and Lynette Dunning and Joanna Brzeszczynska and Kathryn McIntosh and Robin Plevin and S.L. Martin and Sergeant, {Gerard P} and Carl Goodyear and Gary Litherland and John Lockhart and Anne Crilly",

year = "2020",

month = sep,

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doi = "10.1183/13993003.congress-2020.2292",

language = "English",

volume = "56",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "Suppl. 64",

note = "European Respiratory Society International Congress 2020, ERS 2020 ; Conference date: 07-09-2020 Through 09-09-2020",

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Bailo, M, Dunning, L, Brzeszczynska, J, McIntosh, K, Plevin, R, Martin, SL, Sergeant, GP, Goodyear, C, Litherland, G, Lockhart, J & Crilly, A 2020, 'Protease activated receptor 2 (PAR2) antagonism reduces pro-inflammatory cytokine production in bronchial epithelial cells', European Respiratory Journal, vol. 56, no. Suppl. 64, 2292. https://doi.org/10.1183/13993003.congress-2020.2292

TY - JOUR

T1 - Protease activated receptor 2 (PAR2) antagonism reduces pro-inflammatory cytokine production in bronchial epithelial cells

AU - Bailo, Mariarca

AU - Dunning, Lynette

AU - Brzeszczynska, Joanna

AU - McIntosh, Kathryn

AU - Plevin, Robin

AU - Martin, S.L.

AU - Sergeant, Gerard P

AU - Goodyear, Carl

AU - Litherland, Gary

AU - Lockhart, John

AU - Crilly, Anne

PY - 2020/9/7

Y1 - 2020/9/7

N2 - 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.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.

AB - 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.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.

U2 - 10.1183/13993003.congress-2020.2292

DO - 10.1183/13993003.congress-2020.2292

M3 - Meeting abstract

SN - 0903-1936

VL - 56

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - Suppl. 64

M1 - 2292

T2 - European Respiratory Society International Congress 2020

Y2 - 7 September 2020 through 9 September 2020

ER -

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

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