Stimulation of rat endothelial cell transforming growth factor-beta production by bleomycin
| Autor: | Frances M. Wolber, U S Ryan, M Gharaee-Kermani, Sem H. Phan |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
medicine.medical_specialty Pulmonary Fibrosis medicine.medical_treatment Stimulation Bleomycin chemistry.chemical_compound Transforming Growth Factor beta Internal medicine Pulmonary fibrosis medicine Animals RNA Messenger Fibroblast Lung Cells Cultured biology General Medicine Transforming growth factor beta respiratory system medicine.disease Molecular biology Rats Inbred F344 Rats Endothelial stem cell medicine.anatomical_structure Cytokine Endocrinology chemistry Mink biology.protein Collagen Endothelium Vascular Transforming growth factor beta production Research Article |
| Zdroj: | Journal of Clinical Investigation. 87:148-154 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci114964 |
| Popis: | This study examines the hypothesis that mediators from lung endothelial cells could promote lung collagen synthesis in pulmonary fibrosis. Since bleomycin induces pulmonary fibrosis in humans and animals, the effects of this drug on endothelial cells were examined. Endothelial cell conditioned media were prepared in the presence of various doses of bleomycin, and tested for their ability to stimulate lung fibroblast collagen synthesis. The results show a dose-dependent stimulation of endothelial cell secretion of collagen synthesis stimulatory activity by bleomycin, which peaked at a dose greater than or equal to 100 ng/ml. Stimulation was selective for collagenous protein synthesis. Gel filtration analysis showed most of the activity to reside in fractions with an estimated molecular mass range of 10-27 kD. The activity was inhibited by anti-transforming growth factor-beta (TGF-beta)antibody, but not by nonimmune control IgG. The presence of TGF-beta was confirmed using the mink lung epithelial cell assay. Northern blotting revealed significant increases in TGF-beta mRNA in bleomycin-stimulated endothelial cells. Thus in vitro stimulation of endothelial cells by bleomycin upregulates TGF-beta production, presumably by increased transcription. In view of the chemotactic and matrix synthesis stimulatory properties of this cytokine, such an increase in TGF-beta production may play an important role in bleomycin-induced pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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