Particulate-cell interactions and pulmonary cytokine expression.

Abstract

The type II cell plays an important role in the response of the alveolar epithelium after lung injury through its synthesis and secretion of pulmonary surfactant, and by acting as the stem cell for the replacement of damaged type I epithelial cells. The nonciliated bronchiolar epithelial (Clara) cell is thought to play a similar role during repair of the bronchiolar epithelium. Recent evidence has suggested that epithelial cells may participate in aspects of the inflammatory response and regulation of fibroblast growth during pulmonary fibrosis through the production of and response to specific growth factors and cytokines. The cellular and molecular responses of epithelial cells and how they lead to the progression of events that defines the pulmonary parenchymal response to a class of particles is unclear. We used particles differing in size, chemical composition, and fibrogenicity in vivo and in vitro to elucidate early changes in proinflammatory and profibrotic cytokine and antioxidant gene expression in lung cells. Early increases in mRNA and protein for the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha have been observed in epithelial cells following exposure. These are accompanied by changes in specific epithelial genes including surfactant protein C and Clara cell secretory protein. The data indicate that effects on the epithelium are due to direct interactions with particles, not a result of macrophage-derived mediators, and suggest a more significant role in the overall pulmonary response than previously suspected. These results suggest that type II cell growth factor production may be significant in the pathogenesis of pulmonary fibrosis.