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Updated: Aug 30, 2026
Modeling Dysplastic and Functional Lung Alveolar Repair after Influenza Infection
Published on: September 19, 2025
Altered expression and in vivo lung function of protease-activated receptors during influenza A virus infection in
Rommel S Lan1, Geoffrey A Stewart, Roy G Goldie
1School of Medicine and Pharmacology, Faculty of Medicine and Dentistry, University of Western Australia, Perth, 6009 W. A., Australia.
Abstract:
Protease-activated receptors (PARs) are widely distributed in human airways, and recent evidence indicates a role for PARs in the pathophysiology of inflammatory airway disease. To further investigate the role of PARs in airway disease, we determined the expression and function of PARs in a murine model of respiratory tract viral infection. PAR-1, PAR-2, PAR-3, and PAR-4 mRNA and protein were expressed in murine airways, and confocal microscopy revealed colocalization of PAR-2 and cyclooxygenase (COX)-2 immunostaining in basal tracheal epithelial cells. Elevated levels of PAR immunostaining, which was particularly striking for PAR-1 and PAR-2, were observed in the airways of influenza A/PR-8/34 virus-infected mice compared with sham-infected mice. Furthermore, increased PAR-1 and PAR-2 expression was associated with significant changes in in vivo lung function responses. PAR-1 agonist peptide potentiated methacholine-induced increases in airway resistance in anesthetized sham-infected mice (and in indomethacin-treated, virus-infected mice), but no such potentiation was observed in virus-infected mice. PAR-2 agonist peptide transiently inhibited methacholine-induced bronchoconstriction in sham-infected mice, and this effect was prolonged in virus-infected mice. These findings suggest that during viral infection, the upregulation of PARs in the airways is coupled to increased activation of COX and enhanced generation of bronchodilatory prostanoids.
Insights
Protease-activated receptors (PARs) are upregulated in airways during viral infections. Their activation influences lung function by modulating cyclooxygenase (COX) pathways, impacting airway resistance and bronchoconstriction.
Area of Science:
- Immunology
- Respiratory Medicine
- Pharmacology
Background:
- Protease-activated receptors (PARs) are implicated in inflammatory airway diseases.
- Their specific role during viral respiratory infections requires further elucidation.
Purpose of the Study:
- To investigate the expression and function of PARs in a murine model of viral respiratory tract infection.
- To determine the relationship between PARs, cyclooxygenase (COX) activity, and lung function changes during infection.
Main Methods:
- Analysis of PAR-1, PAR-2, PAR-3, and PAR-4 mRNA and protein expression in murine airways.
- Confocal microscopy to assess colocalization of PAR-2 and COX-2.
- Assessment of lung function responses to PAR-1 and PAR-2 agonists in virus-infected and sham-infected mice.
Main Results:
- PAR-1, PAR-2, PAR-3, and PAR-4 were expressed in murine airways.
- Influenza A infection led to elevated PAR-1 and PAR-2 expression, particularly in basal tracheal epithelial cells, with observed colocalization with COX-2.
- PAR-1 and PAR-2 activation differentially modulated airway resistance and bronchoconstriction, with infection prolonging PAR-2-mediated inhibition.
Conclusions:
- Upregulation of PARs in the airways during viral infection is associated with altered lung function.
- PAR activation, in conjunction with COX pathways, likely contributes to the host's response to viral-induced airway inflammation.
- Findings suggest a complex interplay between PARs, COX, and bronchodilatory prostanoid generation during respiratory viral infections.
