Inhibition of gelatinase activity in human airway epithelial cells and fibroblasts by dexamethasone and beclomethasone.

Abstract

The effects of dexamethasone and beclomethasone on gelatinase activity released from lung epithelial cells (A549, NCI-H292 and Calu-3 cell lines and NHBE primary cultures) and human lung fibroblasts (HLF) were investigated. All cells spontaneously released gelatin-degrading activity but the amounts were unaffected by treatment with glucocorticoids. Phorbol myristate acetate (PMA) increased the amount of gelatinase activity in conditioned media prepared from all cell types examined. In epithelial cells, PMA induced the expression of gelatinase B, whereas in HLF the increased gelatinase activity resulted from increased activation of gelatinase A. Dexamethasone and beclomethasone produced concentration-dependent inhibition of PMA-induced gelatinase activity in HLF and epithelial cell lines. In the epithelial cell lines, the inhibition of activity was associated with an attenuation of enzyme induction by PMA. In contrast, primary cultures of human bronchial epithelial cells were unresponsive to dexamethasone at concentrations that were maximally effective at inhibiting gelatinase activity induced in other cells.