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 (PDGF)-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 situ 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 open lung biopsies from patients with IPF showed that IGF-1 was prominently present in pulmonary vessel walls in fibrotic lesions. PDGF and TGF-beta 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-beta mRNA transcripts were not detected in bronchoalveolar epithelial cells.


CONCLUSIONS
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-beta; (2) IGF-1 could be responsible for angiogenesis in IPF; (3) PDGF, TGF-beta are associated with fibroplasia and the deposition of extracellular matrix, as well as vessel remodeling and epithelial cell repopularization.
Cao
B
B
Department of Respiratory Disease, Peking Union Medical College Hospital, Beijing 100730, China. caobin1999@yahoo.com
Guo
Z
Z
Zhu
Y
Y
Xu
W
W
D000328:Adult; D005260:Female; D015870:Gene Expression; D006133:Growth Substances / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I