Transforming growth factor-β (TGF-β) in silicosis

Jaishree Jagirdar, Raymond Begín, André Dufresne, S. Goswami, Theodore C. Lee, William N. Rom

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Silicosis is characterized by fibrosing nodular lesions that may eventually develop into progressive massive fibrosis (PMF). Cytokines (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α] and growth factors insulin-like growth factor-1 [IGF-1] platelet-derived growth factor [PDGF]) have been implicated in the formation of these lesions. TGF-β promotes extracellular matrix accumulation by upregulating collagen and fibronectin gene expression, and inhibits matrix degradation by decreasing secretion of proteases and increasing secretion of protease inhibitors. We hypothesized that TGF-β is associated with matrix deposition and fibrosis in silicosis. To test this hypothesis we studied early and late nodular lesions and PMF (11 cases and two controls) with immunohistochemistry, using rabbit polyclonal antibody to the purified whole molecule of TGF-β in Bouin's fixed lung tissue. This antibody is reactive with both intra- and extracellular forms of TGF-β. In the control lungs, small amounts of TGF-β were present in the bronchial epithelium, macrophages, bronchial and vascular smooth muscle, and bronchial glands. There was minimal to moderate staining in the early silicotic peribronchiolar lesions. In the nodular lesions of silicosis, central hyalinized areas contained the maximum staining for TGF-β. Fibroblasts in the periphery of the nodular lesions were also positive. In acute silicosis, there was marked staining of hyperplastic alveolar epithelium. Macrophages were markedly positive. In the PMF lesions, large areas of scar tissue contained TGF-β. These data suggest a major role for TGF-β in silicosis, particularly in the formation of silicotic nodules and the development of PMF.

Original languageEnglish (US)
Pages (from-to)1076-1081
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume154
Issue number4 I
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Jagirdar, J., Begín, R., Dufresne, A., Goswami, S., Lee, T. C., & Rom, W. N. (1996). Transforming growth factor-β (TGF-β) in silicosis. American Journal of Respiratory and Critical Care Medicine, 154(4 I), 1076-1081. https://doi.org/10.1164/ajrccm.154.4.8887610