The potential role of PDGF, IGF-1, TGF-β expression in idiopathic pulmonary fibrosis

To identify the role of cytokines involved in the development of lung fibrosis in patients with idiopathic pulmonary fibrosis (IPF) Methods Proteins and gene expression of platelet-derived growth factor (PDGF)-A and -B, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta (TGF-β) were measured in alveolar macrophages and open lung biopsies from patients with IPF using immunohistochemistry (IHC) and in situ hybridization (ISH) Results In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B, IGF-1, TGF-β were localized in alveolar macrophages Evaluation of open lung biopsies from patients with IPF showed that IGF-1 was prominently present in pulmonary vessel walls in fibrotic lesions PDGF and TGF-β proteins were localized to hyperplastic bronchio-alveolar epithelial cells, alveolar macrophages, fibroblasts, vascular smooth muscle and endothelial cells Our in situ hybridization results were consistent with that of immunohistochemistry except that PDGF-A and TGF-β mRNA transcripts were not detected in bronchoal-veolar epithelial cells Conclusion These observations suggest that (1) alveolar macrophages play key roles not only in inflammation but also in the fibrotic process by releasing PDGF, IGF-1 and TGF-β; (2) IGF-1 could be responsible for angiogenesis in IPF; (3) PDGF, TGF-β are associated with fibroplasia and the deposition of extracellular matrix, as well as vessel remodeling and epithelial cell repopularization