Pioglitazone, a peroxisome proliferator-activated receptor gamma ligand, suppresses bleomycin-induced acute lung injury and fibrosis
| Autor: | Yasuhiro Aoki, Toshitaka Maeno, Nozomi Aoki, Masashi Arai, Manabu Ueno, Kana Aoyagi, Junichi Nakagawa, Fumiaki Aoki, Tatsuo Suga, Masahiko Kurabayashi, Yoshichika Sando, Yuji Shimizu |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Peroxisome proliferator-activated receptor gamma medicine.medical_specialty Acute Lung Injury Peroxisome proliferator-activated receptor Lung injury Collagen Type I Idiopathic pulmonary fibrosis Bleomycin Transforming Growth Factor beta Internal medicine Pulmonary fibrosis Macrophages Alveolar medicine Animals Humans Hypoglycemic Agents Rats Wistar Idiopathic interstitial pneumonia Lung Cells Cultured chemistry.chemical_classification Pioglitazone business.industry Tumor Necrosis Factor-alpha Connective Tissue Growth Factor Fibroblasts medicine.disease Fibrosis Rats PPAR gamma Endocrinology chemistry Cancer research Peroxisome proliferator-activated receptor delta Thiazolidinediones Peroxisome proliferator-activated receptor alpha business |
| Zdroj: | Respiration; international review of thoracic diseases. 77(3) |
| ISSN: | 1423-0356 |
| Popis: | Background: Peroxisome proliferator-activated receptor-γ (PPARγ) ligands have been shown to possess potent anti-inflammatory actions. Idiopathic interstitial pneumonia is defined as a specific form of chronic fibrosing lung disease characterized by progressive fibrosis which leads to deterioration and destruction of the lungs. Objective: To investigate whether the PPARγ ligand pioglitazone (PGZ) inhibited bleomycin (BLM)-induced acute lung injury and subsequent fibrosis. Methods: BLM was administered intratracheally to Wistar rats which were then treated with PGZ. Rat alveolar macrophages were stimulated with BLM for 6 h with or without PGZ pretreatment for 18 h. MRC-5 cells (human lung fibroblasts) were treated with PGZ for 18 h. After the treatment, the cells were stimulated with transforming growth factor- β (TGF-β) for 6 h. Results: PGZ inhibited BLM-induced acute lung injury and subsequent lung fibrosis when it was administered from day –7. PGZ treatment suppressed the accumulation of inflammatory cells in lungs and the concentration of tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid on day 3. PGZ also inhibited BLM-induced TNF-α production in alveolar macrophages. Furthermore, PGZ inhibited fibrotic changes and an increase in hydroxyproline content in lungs after instillation of BLM, even when PGZ was administered in the period from day 7 to day 28. Northern blot analyses revealed that PGZ inhibited TGF-β-induced procollagen I and connective tissue growth factor (CTGF) expression in MRC-5 cells. Conclusion: These results suggest that activation of PPARγ ameliorates BLM-induced acute inflammatory responses and fibrotic changes at least partly through suppression of TNF-α, procollagen I and CTGF expression. Beneficial effects of this PPARγ ligand on inflammatory and fibrotic processes open new perspectives for a potential role of PPARγ as a molecular target in fibroproliferative lung diseases. |
| Databáze: | OpenAIRE |
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