Silicosis is characterized by fibrosing nodular lesions that may eventually develop into progressive massive
fibrosis (PMF).
Cytokines (
interleukin-1beta [IL-1beta],
tumor necrosis factor-alpha [
TNF-alpha] 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-beta 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-beta 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-beta in Bouin's fixed lung tissue. This antibody is reactive with both intra- and extracellular forms of
TGF-beta. In the control lungs, small amounts of
TGF-beta 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-beta. 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-beta. These data suggest a major role for
TGF-beta in
silicosis, particularly in the formation of silicotic nodules and the development of PMF.