Transforming growth factor β within fibrotic scleroderma lungs

Abstract

purpose, patients, and methods: Since transforming growth factor β (TGFβ) has been implicated as an important mediator of pulmonary fibrosis, we measured TGFβ protein and gene expression in alveolar epithelial lining fluid (ELF) of fibrotic scleroderma lungs sampled by bronchoalveolar lavage (BAL). TGFβ protein was qualitatively examined by Western blot analysis, and quantitatively by radioreceptor assays. Gene expression was evaluated in BAL mononuclear cells by Northern blot analysis with quantification of relative gene expression by densitometric analysis of the autoradiograms. results: Normal and scleroderma subjects had a 24-kd protein that comigrated with defined human TGFβ and immunoreacted with anti-TGFβ antibody. The normal population had a significantly higher average TGFβ concentration (705 pM) compared with the scleroderma subjects (177 pM). The TGFβ gene was expressed in amounts that did not significantly differ between the scleroderma and normal groups. On an individual subject basis, the TGFβ concentration variability did not correlate with variations in BAL cellularity or TGFβ gene expression within the recovered mononuclear cells. conclusions: It is concluded that both normal and fibrotic lungs have TGFβ present at the alveolar epithelial surface. However, in the fibrotic scleroderma lungs, TGFβ protein content and gene expression were not increased at the alveolar epithelial surface. The simultaneous analysis of TGFβ protein content, gene expression, and cellular constituents within individual ELF specimens showed that the cellular components of the ELF do not appear to be major determinants of TGFβ protein concentration at the alveolar epithelial surface.