Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases

Our plain-English summary of Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases, by J. Jagirdar, T.C. Lee, J. Reibman, et al (Environmental Health Perspectives, 1997).

The study

• Authors: J. Jagirdar, T.C. Lee, J. Reibman, L.I. Gold, C. Aston, R. Bégin, W.N. Rom
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1197-203
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, 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 accumulation of extracellular matrix and cell proliferation in asbestos-related diseases.

In plain English

This laboratory study looked for transforming growth factor beta (TGF-beta), a protein involved in scarring, in autopsy lung tissue. The authors stained lung samples from 16 men who had worked in chrysotile asbestos mines and mills in Thetford, Quebec, for an average of 38 years. None had worked in areas where crocidolite exposure may have occurred. All were smokers with lung scarring (pulmonary fibrosis); five also had lung carcinoma and four malignant mesothelioma. Two smokers killed in traffic accidents served as controls. Control lungs showed minimal staining. In the asbestos workers, all three forms of TGF-beta stained intensely in scarred lung tissue, in type II pneumocytes (lung-lining cells that had increased in number), and in pleural fibrosis. In mesothelioma, TGF-beta 1 was found in the surrounding tissue (stroma). One section of the article places TGF-beta 2 mainly in the stroma and another places it mainly in the tumor cells. Both sections find TGF-beta 3 in stroma and tumor cells, but they differ on the amount of staining. The authors concluded the results suggest these forms are important for tissue build-up in asbestosis, pleural fibrosis and malignant mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Autopsy tissue study using immunohistochemistry (antibody staining) for the three forms of TGF-beta, compared with control lungs. Findings were described, not counted or statistically tested.
• Who was studied: 16 men, all smokers, who had worked in the chrysotile asbestos mines and mills of Thetford, Quebec. They were autopsied as part of Quebec Workers' Compensation Board inquiries. Their mean age at death was 71 (standard deviation 8). All had pulmonary fibrosis; 5 also had lung carcinoma and 4 had malignant mesothelioma. The controls were 2 smokers (36 and 48 pack-years) killed in traffic accidents, with no lung fibrosis.
• Exposure: Chrysotile asbestos from work in mines and mills for a mean of 38 years (standard deviation 5). According to their work histories, none had worked in areas with possible crocidolite exposure.
• Main results:
  • In the two control lungs, staining for all three TGF-beta forms was minimal. It was present in the same lung structures, such as macrophages and bronchial lining cells.
  • In the asbestos workers' scarred lungs, all three TGF-beta forms stained intensely in the tissue material (extracellular matrix) of fibrotic areas.
  • In advanced honeycomb lesions, all three forms were found in hyperplastic type II pneumocytes (lung-lining cells that had increased in number) and in cells lining cystic spaces.
  • All three TGF-beta forms stained the tissue material of pleural fibrosis (pleural plaque) intensely.
  • In malignant mesothelioma, TGF-beta 1 staining was found in the stroma, the tissue around the tumor cells.
  • For TGF-beta 2 in mesothelioma, the Results section says stromal cells stained more intensely and tumor cells markedly less. The Discussion says it localized more to the mesothelioma cells than to the stroma.
  • For TGF-beta 3 in mesothelioma, both sections place staining in the stroma and the tumor cells. The Results section says many tumor cells stained positively, while the Discussion describes minimal staining of both.
• The authors' conclusion: The authors concluded that the results suggest TGF-beta forms are important for the accumulation of tissue material (extracellular matrix) in asbestosis, pleural fibrosis and malignant mesothelioma.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Chrysotile, Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytokine, Fibrosis, Pleura, Lung Cancer, Mesothelioma, Immunohistochemistry, Autopsy, Malignant Mesothelioma.

Related studies

• Immunohistochemical localization of transforming growth factor-beta and insulin-like growth factor-I in asbestosis in the sheep model — T.C. Lee, L.I. Gold, et al. (1997)
• Susceptibility to asbestos-induced and transforming growth factor-beta1-induced fibroproliferative lung disease in two strains of mice — G.S. Warshamana, D.A. Pociask, et al. (2002)
• Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats — T.D. Perdue, A.R. Brody (1994)
• Transforming growth factor-beta(1) overexpression in tumor necrosis factor-alpha receptor knockout mice induces fibroproliferative lung disease — J.Y. Liu, P.J. Sime, et al. (2001)
• Reduced tumor necrosis factor-alpha and transforming growth factor-beta1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure — D.M. Brass, G.W. Hoyle, et al. (1999)
• Transforming growth factor-beta 1 (TGF-beta 1)- and beta 2-like activities in malignant pleural effusions caused by malignant mesothelioma or primary lung cancer — J. Maeda, N. Ueki, et al. (1994)

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