Complex Regulatory Role of the TRPA1 Receptor in Acute and Chronic Airway Inflammation Mouse Models

• Published in: International journal of molecular sciences 2020-06, Vol.21 (11), p.4109
• Main Authors: Hajna, Zsófia, Csekő, Kata, Kemény, Ágnes, Kereskai, László, Kiss, Tamás, Perkecz, Anikó, Szitter, István, Kocsis, Béla, Pintér, Erika, Helyes, Zsuzsanna
• Format: Article
• Language: English
• Subjects: Acrolein; Animal models; Animals; Asthma; Bronchitis; Bronchitis, Chronic - chemically induced; Bronchitis, Chronic - physiopathology; Bronchoalveolar Lavage Fluid; Capsaicin; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette Smoking - adverse effects; Cigarettes; COPD; Disease Models, Animal; Edema; Emphysema; Endothelial cells; Endotoxins; Female; Fibroblasts; Granulocytes; Hyperreactivity; Inflammation; Kinases; Lipopolysaccharides; Lipopolysaccharides - toxicity; LPS; Lung - metabolism; Lung - pathology; Lymphocytes; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Neuropeptides; Neutrophils; Nicotine; Peroxidase; Peroxidase - metabolism; Physiology; Plethysmography; Plethysmography, Whole Body; Pneumonia - chemically induced; Pneumonia - physiopathology; Pneumonitis; Proteins; Pulmonary Emphysema - chemically induced; Pulmonary Emphysema - metabolism; Pulmonary Emphysema - pathology; Respiration; Respiratory Function Tests; Respiratory tract; Respiratory tract diseases; Smooth muscle; Transient receptor potential proteins; TRPA1 Cation Channel - genetics; TRPA1 Cation Channel - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21114109

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 gene-deleted ( ) mice. Acute pneumonitis was evoked by intranasal 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 mice. LPS-induced bronchial hyperreactivity, myeloperoxidase activity, frequency-decrease were significantly greater in mice. CSE significantly decreased tidal volume, minute ventilation, peak inspiratory/expiratory flows in wildtypes, but not in mice. CSE remarkably increased the mean linear intercept (histopathology), as an emphysema indicator after 2 months in wildtypes, but only after 4 months in 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.