PARTICULATE-CELL INTERACTIONS AND PULMONARY CYTOKINE EXPRESSION

The type II cell plays an important role in the response of the alveol ar epithelium after lung injury through its synthesis and secretion oi pulmonary surfactant, and by acting as the stem cell for the replacem ent of damaged type I epithelial cells, The nonciliated bronchiolar ep ithelial (Clara) cell is thought to play a similar role during repair of the bronchiolar epithelium. Recent evidence has suggested that epit helial cells may participate in aspects of the inflammatory response a nd regulation of fibroblast growth during pulmonary fibrosis through t he production of ard response to specific growth factors and cytokines . The cellular and molecular responses of epithelial cells and how the y lead to the progression of events that defines the pulmonary parench ymal response to a class of particles is unclear. We used particles di ffering in size, chemical composition, and fibrogenicity in vivo and i n vitro to elucidate early changes in proinflammatory and profibrotic cytokine and antioxidant gene expression in lung cells. Early increase s in mRNA and protein for the proinflammatory cytokines interleukin (I L)-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 epithel ium are due to direct interactions with particles, not a result of mac rophage-derived mediators, and suggest a more significant roll in the overall pulmonary response than previously suspected. These results su ggest that type II cell growth factor production may be significant in the pathogenesis of pulmonary fibrosis.