Complex regulatory role of the trpa1 receptor in acute and chronic airway inflammation mouse models

Zsófia Hajna, Kata Csekő, Ágnes Kemény, László Kereskai, Tamás Kiss, Anikó Perkecz, István Szitter, Béla Kocsis, Erika Pintér, Zsuzsanna Helyes

Research output: Contribution to journalArticle

Abstract

The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channel expressed on capsaicin-sensitive afferents, immune and endothelial cells is activated by inflammatory mediators and exogenous irritants, e.g., endotoxins, nicotine, crotonaldehyde and acrolein. We investigated its involvement in acute and chronic pulmonary inflammation using Trpa1 gene-deleted (Trpa1−/−) mice. Acute pneumonitis was evoked by intranasal Escherichia coli endotoxin (lipopolysaccharide: LPS) administration, chronic bronchitis by daily cigarette smoke exposure (CSE) for 4 months. Frequency, peak inspiratory/expiratory flows, minute ventilation determined by unrestrained whole-body plethysmography were significantly greater, while tidal volume, inspiratory/expiratory/relaxation times were smaller in Trpa1−/− mice. LPS-induced bronchial hyperreactivity, myeloperoxidase activity, frequency-decrease were significantly greater in Trpa1−/− mice. CSE significantly decreased tidal volume, minute ventilation, peak inspiratory/expiratory flows in wildtypes, but not in Trpa1−/− mice. CSE remarkably increased the mean linear intercept (histopathology), as an emphysema indicator after 2 months in wildtypes, but only after 4 months in Trpa1−/− mice. Semiquantitative histopathological scores were not different between strains in either models. TRPA1 has a complex role in basal airway function regulation and inflammatory mechanisms. It protects against LPS-induced acute pneumonitis and hyperresponsiveness, but is required for CSE-evoked emphysema and respiratory deterioration. Further research is needed to determine TRPA1 as a potential pharmacological target in the lung.

Original languageEnglish
Article number4109
Pages (from-to)1-21
Number of pages21
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
Publication statusPublished - Jun 1 2020

Keywords

  • Bronchitis
  • COPD
  • Cigarette smoke
  • Emphysema
  • LPS
  • Pneumonitis
  • Whole body plethysmography

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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