TGF-BETA(1), BUT NOT TGF-BETA(2) OR TGF-BETA(3), IS DIFFERENTIALLY PRESENT IN EPITHELIAL-CELLS OF ADVANCED PULMONARY FIBROSIS - AN IMMUNOHISTOCHEMICAL STUDY

Although it is recognized that three isoforms of transforming growth f actor-beta (TGF-beta) exist in mammals, their expression, distribution , and function in injury and repair are not well characterized. Using immunohistochemistry and antibodies to synthetic peptides of TGF-beta( 1), TGF-beta(2), and TGF-beta(3), we determined the distribution of TG F-beta isoforms in lung sections with acute and chronic lesions of idi opathic pulmonary fibrosis (IPF), chronic asbestosis and hypersensitiv ity pneumonitis, as well as non-specific pneumonitis. In lung sections with advanced pulmonary fibrosis and honeycombing, irrespective of th e diagnosis, TGF-beta(1) was prominently expressed in epithelial cells and macrophages and was found to be associated with the extracellular matrix. In lungs with early lesions of IPF and only inflammatory chan ges, TGF-beta(1) was present in alveolar macrophages but TGF-beta(1) w as not present in epithelial cells. Small amounts of matrix-associated TGF-beta(1) were present subepithelially in areas of lung sections fr om patients with IPF with minimal inflammation and no fibrosis. In nor mal lungs with no evidence of inflammation or fibrosis TGF-beta(1) was not seen in alveolar macrophages, epithelial cells, or extracellularl y, TGF-beta(2) and TGF-beta(3) were expressed in alveolar macrophages, epithelial cells, and smooth muscle cells of vessels and bronchi of n ormal lungs and lungs with both inflammatory and fibrotic changes. Our findings suggest that while TGF-beta(2) and TGF-beta(3) are ubiquitou sly expressed in the lung, TGF-beta(1) is expressed in epithelial cell s of fibrotic lungs where the presence of TGF-beta(1) is not disease-s pecific but an indication of the chronicity of the injury.