RRC ID 56610
Author Kuwabara Y, Kobayashi T, D'Alessandro-Gabazza CN, Toda M, Yasuma T, Nishihama K, Takeshita A, Fujimoto H, Nagao M, Fujisawa T, Gabazza EC.
Title Role of Matrix Metalloproteinase-2 in Eosinophil-Mediated Airway Remodeling.
Journal Front Immunol
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.
Volume 9
Pages 2163
Published 2018-9-20
DOI 10.3389/fimmu.2018.02163
PMID 30294331
PMC PMC6158585
MeSH Adoptive Transfer Airway Remodeling / drug effects Airway Remodeling / immunology* Animals Asthma / immunology* Asthma / pathology Cell Culture Techniques Cell Differentiation / immunology Cell Line Cell Movement / drug effects Cell Movement / immunology Coculture Techniques Eosinophils / immunology* Eosinophils / metabolism Eosinophils / transplantation Female Humans Matrix Metalloproteinase 2 / genetics Matrix Metalloproteinase 2 / immunology Matrix Metalloproteinase 2 / metabolism* Matrix Metalloproteinase Inhibitors / pharmacology Mice Mice, Inbred C57BL Mice, Transgenic Myofibroblasts / physiology*
IF 4.716
Times Cited 6
Human and Animal Cells HFL-I(RCB0521)