IMMUNOHISTOCHEMICAL LOCALIZATION OF TRANSFORMING-GROWTH-FACTOR-BETA ISOFORMS IN ASBESTOS-RELATED DISEASES

Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processe s because of its ability to induce extracellular matrix proteins and m odulate the growth and immune function of many cell types. These effec ts are important in inflammatory disorders with fibrosis and cancer. T he asbestos-related diseases are characterized by fibrosis in the lowe r respiratory tract and pleura and increased occurrence oi lung cancer and mesothelioma. We performed immunohistochemistry with isoform-spec ific antibodies to the three TGF-beta isoforms on 16 autopsy lungs fro m Quebec, Canada, asbestos miners and millers. There was increased imm unolocalization of all three TGF-beta isoforms :n the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocy tes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothel ioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accu mulation of extracellular matrix and cell proliferation in asbestos-re lated diseases.