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 asthma, viral infection, acute lung injury, and fibrotic lung disease. Activated T lymphocytes release cytokines such as interferon-gamma (IFN-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. Interestingly, the corticosteroid dexamethasone was the most potent inhibitor of IFN-gamma- and IFN-gamma plus anti-Fas-induced apoptosis. IFN-gamma induced expression of an effector of apoptosis, the cysteine protease interleukin-1 beta-converting enzyme, in A549 cells. Dexamethasone, in contrast, induced expression of an inhibitor of apoptosis, human inhibitor of apoptosis (hIAP-1), also known as cIAP2. We suggest that the inhibition of epithelial cell apoptosis by corticosteroids may be one mechanism by which they suppress the inflammatory response.
Wen
L P
LP
Department of Pulmonary and Critical Care Medicine, Stanford University, California 94305-5236, USA.
Madani
K
K
Fahrni
J A
JA
Duncan
S R
SR
Rosen
G D
GD
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D053222:Fas Ligand Protein; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D003907:Dexamethasone; D007371:Interferon-gamma; D004247:DNA; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D013936:Thymidine