DEXAMETHASONE INHIBITS LUNG EPITHELIAL-CELL APOPTOSIS INDUCED BY IFN-GAMMA AND FAS

Lung epithelium plays a central role in modulation of the inflammatory response and in lung repair. Airway epithelial cells are targets in a sthma, viral infection, acute lung injury, and fibrotic lung disease. Activated T lymphocytes release cytokines such as interferon-gamma (IF N-gamma) that can cooperate with apoptotic signaling pathways such as the Fas-APO-1 pathway to induce apoptosis of damaged epithelial cells. We report that IFN-gamma alone and in combination with activation of the Fas pathway induced apoptosis in A549 lung epithelial cells. Inter estingly, the corticosteroid dexamethasone was the most potent inhibit or of IFN-gamma-and IFN-gamma plus anti-Fas-induced apoptosis. IFN-gam ma induced expression of an effector of apoptosis, the cysteine protea se interleukin-1 beta-converting enzyme, in A549 cells. Dexamethasone, in contrast, induced expression of an inhibitor of apoptosis, human i nhibitor of apoptosis (hIAP-1), also known as cIAP2. We suggest that t he inhibition of epithelial cell apoptosis by corticosteroids may be o ne mechanism by which they suppress the inflammatory response.