論文 - 詳細
| RRC ID | 56610 |
|---|---|
| 著者 | Kuwabara Y, Kobayashi T, D'Alessandro-Gabazza CN, Toda M, Yasuma T, Nishihama K, Takeshita A, Fujimoto H, Nagao M, Fujisawa T, Gabazza EC. |
| タイトル | Role of Matrix Metalloproteinase-2 in Eosinophil-Mediated Airway Remodeling. |
| ジャーナル | 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. |
| 巻・号 | 9 |
| ページ | 2163 |
| 公開日 | 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 |
| 引用数 | 6 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HFL-I(RCB0521) |