Pharmacological blockade of protease-Activated Receptor 2 improves airway remodeling and lung inflammation in experimental allergic asthma
Document title: Pharmacological blockade of protease-Activated Receptor 2 improves airway remodeling and lung inflammation in experimental allergic asthma
Journal: Brazilian Journal of Pharmaceutical Sciences
Database: PERIÓDICA
System number: 000451809
ISSN: 1984-8250
Authors: 1
2
3
3
2
3
4
4
Institutions: 1Universidade Federal de Ouro Preto, Instituto de Ciencias Exatas e Biologicas, Ouro Preto, Minas Gerais. Brasil
2Universidade Federal de Minas Gerais, Departamento de Patologia Geral, Belo Horizonte, Minas Gerais. Brasil
3Universidade Federal de Minas Gerais, Departamento de Fisiologia e Biofisica, Belo Horizonte, Minas Gerais. Brasil
4Universidade Federal de Minas Gerais, Instituto de Ciencias Biologicas, Belo Horizonte, Minas Gerais. Brasil
Year:
Volumen: 58
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract Protease-activated receptors (PARs) are metabotropic G-protein-coupled receptors that are activated via proteolytic cleavage of a specific sequence of amino acids in their N-terminal region. PAR2 has been implicated in mediating allergic airway inflammation. This study aims to study the effect of PAR2 antagonist ENMD1068in lung inflammation and airway remodeling in experimental asthma. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with ENMD1068 1 hour before each OVA challenge. Bronchoalveolar lavage fluid (BALF) was collected, and the lungs were removed at different time intervals after OVA challenge to analyze inflammation, airway remodeling and airway hyperresponsiveness. Ovalbumin promoted leukocyte infiltration into BALF in a PAR2-dependent manner. ENMD1068 impaired eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity in the lung parenchyma into BALF and reduced the loss of dynamic pulmonary compliance, lung resistance in response to methacholine, mucus production, collagen deposition and chemokine (C-C motif) ligand 5 expression compared to those in OVA-challenged mice. We propose that proteases released after an allergen challenge may be crucial to the development of allergic asthma in mice, and PAR2 blockade may be useful as a new pharmacological approach for the treatment of airway allergic diseases
Disciplines: Medicina
Keyword: Medicina experimental,
Farmacología,
Neumología,
Bloqueo farmacológico,
Receptores químicos,
Proteasas,
Alergia respiratoria,
Asma,
Inflamación,
Pulmones
Keyword: Experimental medicine,
Pharmacology,
Pneumology,
Pharmacological blockade,
Chemical receptors,
Proteases,
Respiratory allergy,
Asthma,
Lungs,
Inflammation
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