1. Macrophage-secreted TSLP and MMP9 promote bleomycin-induced pulmonary fibrosis.
- Author
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Li G, Jin F, Du J, He Q, Yang B, and Luo P
- Subjects
- Animals, Cell Line, Cell Movement, Coculture Techniques, Disease Models, Animal, Epithelial-Mesenchymal Transition, Female, Fibroblasts pathology, Lung pathology, Macrophages, Alveolar pathology, Mice, Inbred ICR, Pulmonary Fibrosis chemically induced, Pulmonary Fibrosis pathology, Rats, Wistar, Signal Transduction, Time Factors, Thymic Stromal Lymphopoietin, Bleomycin, Cytokines metabolism, Fibroblasts enzymology, Lung enzymology, Macrophages, Alveolar enzymology, Matrix Metalloproteinase 9 metabolism, Pulmonary Fibrosis enzymology
- Abstract
Idiopathic pulmonary fibrosis is a pathological result of dysfunctional repair response to tissue injury, leading to chronically impaired gas exchange and death. Macrophages are believed to be critical in this disease pathogenesis; However, the exact mechanisms remain enigmatic. Here, we demonstrated that macrophages might contribute to pulmonary fibrosis at the early stage because the aggregation of macrophages appeared earlier than epithelial-mesenchymal transition and fibrosis in mouse and rat experimental models of pulmonary fibrosis. It has been found that macrophages could promote epithelial-mesenchymal transition of alveolar epithelial cells and fibroblast migration in co-culture models between macrophages and alveolar epithelial cells/fibroblasts. Importantly, we used protein micro array to analyze the cytokines that were altered after bleomycin treatment. Only thymic stromal lymphopoietin and matrix metalloproteinase 9 were significantly increased. We further confirmed that TSLP participated in the macrophage-induced epithelial-mesenchymal transition of alveolar epithelial cells using a TSLP recombinant protein. MMP9 was also involved in macrophage-induced fibroblast migration, which can be reversed by an inhibitor of MMP9. Collectively, these findings explained the underlying mechanisms of macrophage-promoted pulmonary fibrosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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