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Macrophage-secreted TSLP and MMP9 promote bleomycin-induced pulmonary fibrosis.
- Source :
-
Toxicology & Applied Pharmacology . Mar2019, Vol. 366, p10-16. 7p. - Publication Year :
- 2019
-
Abstract
- 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. Highlights • Macrophages contribute to bleomycin-induced pulmonary fibrosis • TSLP and MMP9 may be pivotal cytokines secreted by macrophages • TSLP may induce epithelial-mesenchymal transition of alveolar epithelial cells • MMP9 is involved in macrophage-induced fibroblast migration [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0041008X
- Volume :
- 366
- Database :
- Academic Search Index
- Journal :
- Toxicology & Applied Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 134572601
- Full Text :
- https://doi.org/10.1016/j.taap.2019.01.011