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Proteoglycan expression in bleomycin lung fibroblasts: role of transforming growth factor-beta(1) and interferon-gamma.
Proteoglycan expression in bleomycin lung fibroblasts: role of transforming growth factor-beta(1) and interferon-gamma.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2002 Oct; Vol. 283 (4), pp. L806-14. - Publication Year :
- 2002
-
Abstract
- Bleomycin (BM)-induced pulmonary fibrosis involves excess production of proteoglycans (PGs). Because transforming growth factor-beta(1) (TGF-beta(1)) promotes fibrosis, and interferon-gamma (IFN-gamma) inhibits it, we hypothesized that TGF-beta(1) treatment would upregulate PG production in fibrotic lung fibroblasts, and IFN-gamma would abrogate this effect. Primary lung fibroblast cultures were established from rats 14 days after intratracheal instillation of saline (control) or BM (1.5 units). PGs were extracted and subjected to Western blot analysis. Bleomycin-exposed lung fibroblasts (BLF) exhibited increased production of versican (VS), heparan sulfate proteoglycan (HSPG), and biglycan (BG) compared with normal lung fibroblasts (NLF). Compared with NLF, BLF released significantly increased amounts of TGF-beta(1). TGF-beta(1) (5 ng/ml for 48 h) upregulated PG expression in both BLF and NLF. Incubation of BLF with anti-TGF-beta antibody (1, 5, and 10 microg/ml) inhibited PG expression in a dose-dependent manner. Treatment of BLF with IFN-gamma (500 U. ml(-1) x 48 h) reduced VS, HSPG, and BG expression. Furthermore, IFN-gamma inhibited TGF-beta(1)-induced increases in PG expression by these fibroblasts. Activation of fibroblasts by TGF-beta(1) promotes abnormal deposition of PGs in fibrotic lungs; downregulation of TGF-beta(1) by IFN-gamma may have potential therapeutic benefits in this disease.
- Subjects :
- Animals
Antibodies pharmacology
Antimetabolites, Antineoplastic pharmacology
Biglycan
Bleomycin pharmacology
Cell Division physiology
Cell Survival physiology
Cells, Cultured
Chondroitin Sulfate Proteoglycans analysis
Chondroitin Sulfate Proteoglycans biosynthesis
Extracellular Matrix Proteins
Fibroblasts cytology
Fibroblasts drug effects
Heparan Sulfate Proteoglycans analysis
In Vitro Techniques
Lectins, C-Type
Male
Proteoglycans analysis
Proteoglycans biosynthesis
Rats
Rats, Sprague-Dawley
Transforming Growth Factor beta immunology
Transforming Growth Factor beta pharmacology
Transforming Growth Factor beta1
Up-Regulation physiology
Versicans
Fibroblasts metabolism
Heparan Sulfate Proteoglycans biosynthesis
Interferon-gamma physiology
Pulmonary Fibrosis metabolism
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1040-0605
- Volume :
- 283
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 12225958
- Full Text :
- https://doi.org/10.1152/ajplung.00061.2002