Bronchial epithelial cell matrix production in response to silica and basic fibroblast growth factor

Background: Previous studies show that macrophages, lung fibroblasts, and t heir soluble mediators are responsible for the onset and development of pul monary fibrosis. This study was conducted to determine whether airway epith elial cells are also directly involved in response to fibrogenic agents and consequently in the pathogenesis of lung fibrosis. To verify the hypothesi s, we determined whether silica acts directly on human bronchial epithelial cells by stimulating cytokine and growth factor release and by modifying m atrix production Materials and Methods: An SV40 large T antigen-transformed human airway epi thelial cell line, 16HBE14o (16HBE), was used. The expression profile of so me proinflammatory interleukins (ILs), such as IL-1 alpha, IL-1 beta and IL -6 and their modulation by silica, were evaluated by polymerase chain react ion (PCR) analysis. Transforming growth factor beta (TGF beta) and basic fi broblast growth factor (bFGF) mRNA levels were tested by Northern blotting in the presence and in the absence of silica. The silica- and/or bFGF-induc ed effects on matrix components (total proteins, collagen, and fibronectin) were also evaluated using radiolabeled precursors. Results: The results demonstrated 16HBE internalized silica particles. Sili ca induced a little IL-6 secretion, without affecting IL-1 and TGF beta iso form production and strongly stimulated bFGF mRNA level and bFGF protein se cretion. Silica also induced changes in 16HBE production of total proteins, collagen, and fibronectin production. When added in combination with the g rowth factor, it strengthened bFGF stimulation of matrix component secretio n. Conclusions: These results support the hypothesis that the changes in matri x components are due to a direct effect of silica on bronchial epithelial c ells. Silica-induced oversecretion of bFGF suggests that autocrine and para crine differentiation loops for bFGF may also be operative and that these m echanisms may be involved in the pathogenesis of pulmonary fibrosis. In the future, cytokine-directed therapeutic strategies might find a place in cli nical practice.