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

Objective 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 (PDG F)-A and -B, insulin-like growth factor 1 (IGF-1), and transforming growth factor beta (TGF-beta) were measured in alveolar macrophages and open lung biopsies from patients with IPF using immunohistochemistry (IHC) and in sit u hybridization (ISH). Results In specimens of bronchoalveolar lavage fluid (BALF), PDGF-A, PDGF-B , IGF-1, TGF-beta were localized in alveolar macrophages. Evaluation of ope n lung biopsies from patients with IPF showed that IGF-1 was prominently pr esent in pulmonary vessel walls in fibrotic lesions. PDGF and TGF-beta prot eins were localized to hyperplastic bronchio-alveolar epithelial cells, alv eolar macrophages, fibroblasts, vascular smooth muscle and endothelial cell s. Our in situ hybridization results were consistent with mar or immunohist ochemistry except that PDGF-A and TGF-beta mRNA transcripts were not detect ed in bronchoalveolar epithelial cells. Conclusion These observations suggest that (1) alveolar macrophages play ke y roles not only in inflammation but also in the fibrotic process py releas ing PDGF, IGF-1 and TGF-beta; (2) IGF-1 could be responsible for angiogenes is in IPF; (3) PDGF, TGF-beta are associated with fibroplasia and the depos ition of extracellular matrix, as well as Vessel remodeling and epithelial cell repopularization.