Role of Matrix Metalloproteinase-2 in Eosinophil-Mediated Airway Remodeling.
Front Immunol
; 9: 2163, 2018.
Article
em En
| MEDLINE
| ID: mdl-30294331
ABSTRACT
Airway remodeling is responsible for the progressive decline of lung function in bronchial asthma. Matrix metalloproteinase-2 and fibroblast-to-myofibroblast transition are involved in tissue remodeling. Here we evaluated whether eosinophils play a role in fibroblasts-to-myofibroblasts transition and in the expression of matrix metalloproteinase-2. We co-cultured human eosinophils with human fetal lung fibroblast-1 cells, assessed the expression of remodeling-associated molecules by immunoassays and polymerase-chain reaction, and eosinophils-mediated migration of human fetal lung fibroblast-1 cells using a Boyden chamber. To clarify the participation of matrix metalloproteinase-2 in airway remodeling we administered bone marrow-derived eosinophils by intra-tracheal route to transgenic mice overexpressing the human matrix metalloproteinase-2. The expression of α-smooth muscle actin significantly increased in human fetal lung fibroblast-1 cells co-cultured with human eosinophils compared to controls. There was enhanced expression of matrix metalloproteinase-2 during fibroblast-to-myofibroblast transition. An inhibitor of matrix metalloproteinases blocked eosinophils-associated fibroblast-to-myofibroblast transition and increased migration of fibroblasts. The human matrix metalloproteinase-2 transgenic mice receiving adoptive transfer of mouse eosinophils exhibited increased inflammation and advanced airway remodeling compared to wild type mice. This study demonstrated that eosinophils induce fibroblast-to-myofibroblast transition, secretion of matrix metalloproteinase-2, accelerated migration of fibroblasts, and promote matrix metalloproteinase-2-related airway remodeling. These findings provide a novel mechanistic pathway for eosinophil-associated airway remodeling in bronchial asthma.
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Base de dados:
MEDLINE
Assunto principal:
Asma
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Metaloproteinase 2 da Matriz
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Eosinófilos
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Remodelação das Vias Aéreas
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Miofibroblastos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão