Proteinase activated receptor 2 (PAR2) modulation of airway smooth muscle function

Kimberly Black, Andrew MacKenzie, Lynette Dunning, Anne Crilly, Lorcan McGarvey, Keith Thornbury, Carl Goodyear, John Lockhart, Gary Litherland

Research output: Contribution to journalMeeting Abstract

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Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive lung condition characterised by airflow obstruction and irreversible lung damage. Hyperactivity and growth of airway smooth muscle (ASM) limit airflow and are key features of COPD. Proteinase activated receptor-2 (PAR2) is a key modulator of inflammatory responses in respiratory disease, such as asthma and promotes ASM relaxation. However, the precise role of the receptor in ASM in conditions such as COPD is not well understood (1). The aim of this study was to establish an ex vivo murine airway myograph assay for investigation of functional PAR2 responses to challenges relevant in COPD pathology. To achieve this, murine trachea and bronchi tissue was either mounted on a wire myograph for dynamic tension recording or processed for immunohistochemical localisation of PAR2 expression. PAR2 was present on both murine airway and lung tissue. Stimulation of PAR2 with trypsin (10 U ml-1) or activating peptide was observed to induce relaxation responses in ASM tension. Taken together this data verifies that PAR2 is present and functional in murine airways, and ex vivo modulation alters ASM tone. Ongoing experiments will investigate the effect of disease-relevant insults on this modulation in wild type and PAR2-deficient airways.
Original languageEnglish
Pages (from-to)S249-S249
Number of pages1
JournalIrish Journal of Medical Science
Volume187
Issue numberSupplement 8
DOIs
Publication statusPublished - 8 Oct 2018

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PAR-2 Receptor
Smooth Muscle
Chronic Obstructive Pulmonary Disease
Lung
Muscle Tonus
Muscle Relaxation
Bronchi
Trachea
Trypsin
Asthma
Pathology
Peptides
Growth

Keywords

  • PAR2
  • COPD
  • BREATH
  • interreg va
  • SEUPB
  • airway smooth muscle

Cite this

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title = "Proteinase activated receptor 2 (PAR2) modulation of airway smooth muscle function",
abstract = "Chronic obstructive pulmonary disease (COPD) is a progressive lung condition characterised by airflow obstruction and irreversible lung damage. Hyperactivity and growth of airway smooth muscle (ASM) limit airflow and are key features of COPD. Proteinase activated receptor-2 (PAR2) is a key modulator of inflammatory responses in respiratory disease, such as asthma and promotes ASM relaxation. However, the precise role of the receptor in ASM in conditions such as COPD is not well understood (1). The aim of this study was to establish an ex vivo murine airway myograph assay for investigation of functional PAR2 responses to challenges relevant in COPD pathology. To achieve this, murine trachea and bronchi tissue was either mounted on a wire myograph for dynamic tension recording or processed for immunohistochemical localisation of PAR2 expression. PAR2 was present on both murine airway and lung tissue. Stimulation of PAR2 with trypsin (10 U ml-1) or activating peptide was observed to induce relaxation responses in ASM tension. Taken together this data verifies that PAR2 is present and functional in murine airways, and ex vivo modulation alters ASM tone. Ongoing experiments will investigate the effect of disease-relevant insults on this modulation in wild type and PAR2-deficient airways.",
keywords = "PAR2, COPD, BREATH, interreg va, SEUPB, airway smooth muscle",
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year = "2018",
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Proteinase activated receptor 2 (PAR2) modulation of airway smooth muscle function. / Black, Kimberly; MacKenzie, Andrew; Dunning, Lynette; Crilly, Anne; McGarvey, Lorcan; Thornbury, Keith; Goodyear, Carl; Lockhart, John; Litherland, Gary.

In: Irish Journal of Medical Science, Vol. 187, No. Supplement 8, 08.10.2018, p. S249-S249.

Research output: Contribution to journalMeeting Abstract

TY - JOUR

T1 - Proteinase activated receptor 2 (PAR2) modulation of airway smooth muscle function

AU - Black, Kimberly

AU - MacKenzie, Andrew

AU - Dunning, Lynette

AU - Crilly, Anne

AU - McGarvey, Lorcan

AU - Thornbury, Keith

AU - Goodyear, Carl

AU - Lockhart, John

AU - Litherland, Gary

PY - 2018/10/8

Y1 - 2018/10/8

N2 - Chronic obstructive pulmonary disease (COPD) is a progressive lung condition characterised by airflow obstruction and irreversible lung damage. Hyperactivity and growth of airway smooth muscle (ASM) limit airflow and are key features of COPD. Proteinase activated receptor-2 (PAR2) is a key modulator of inflammatory responses in respiratory disease, such as asthma and promotes ASM relaxation. However, the precise role of the receptor in ASM in conditions such as COPD is not well understood (1). The aim of this study was to establish an ex vivo murine airway myograph assay for investigation of functional PAR2 responses to challenges relevant in COPD pathology. To achieve this, murine trachea and bronchi tissue was either mounted on a wire myograph for dynamic tension recording or processed for immunohistochemical localisation of PAR2 expression. PAR2 was present on both murine airway and lung tissue. Stimulation of PAR2 with trypsin (10 U ml-1) or activating peptide was observed to induce relaxation responses in ASM tension. Taken together this data verifies that PAR2 is present and functional in murine airways, and ex vivo modulation alters ASM tone. Ongoing experiments will investigate the effect of disease-relevant insults on this modulation in wild type and PAR2-deficient airways.

AB - Chronic obstructive pulmonary disease (COPD) is a progressive lung condition characterised by airflow obstruction and irreversible lung damage. Hyperactivity and growth of airway smooth muscle (ASM) limit airflow and are key features of COPD. Proteinase activated receptor-2 (PAR2) is a key modulator of inflammatory responses in respiratory disease, such as asthma and promotes ASM relaxation. However, the precise role of the receptor in ASM in conditions such as COPD is not well understood (1). The aim of this study was to establish an ex vivo murine airway myograph assay for investigation of functional PAR2 responses to challenges relevant in COPD pathology. To achieve this, murine trachea and bronchi tissue was either mounted on a wire myograph for dynamic tension recording or processed for immunohistochemical localisation of PAR2 expression. PAR2 was present on both murine airway and lung tissue. Stimulation of PAR2 with trypsin (10 U ml-1) or activating peptide was observed to induce relaxation responses in ASM tension. Taken together this data verifies that PAR2 is present and functional in murine airways, and ex vivo modulation alters ASM tone. Ongoing experiments will investigate the effect of disease-relevant insults on this modulation in wild type and PAR2-deficient airways.

KW - PAR2

KW - COPD

KW - BREATH

KW - interreg va

KW - SEUPB

KW - airway smooth muscle

U2 - 10.1007/s11845-018-1898-7

DO - 10.1007/s11845-018-1898-7

M3 - Meeting Abstract

VL - 187

SP - S249-S249

JO - Irish Journal of Medical Science

JF - Irish Journal of Medical Science

SN - 0021-1265

IS - Supplement 8

ER -