Biosynthesis of alpha(1)-proteinase inhibitor by human lung-derived epithelial cells

Destruction of components of the extracellular matrix of the lung by neutrophil elastase is believed to be a critical event in the development of obstructive lung disease. The local synthesis of alpha(1)-proteinase inhibitor, the controlling inhibitor of this enzyme, may provide a partial mechanism for neutrophil elastase regulation, especially during inflammation, when proteolytic enzymes are released from phagocytes. In this study, we show that lung-derived epithelial cells not only have the capacity to synthesize functional alpha(1)-PI but also to increase the rate of its production when stimulated by specific inflammatory mediators, including oncostatin M, interleukin-1, and the glucocorticoid analogue, dexamethasone.