Upregulation of Fas-signalling molecules in lung epithelial cells from patients with idiopathic pulmonary fibrosis

The caspase cascade is an executioner of apoptosis, mediated by Fas, Fas-as sociating protein with death domain (FADD) interacts with Fas and initiates apoptosis through activating caspase-8, It has previously been demonstrate d that the Fas-Fas ligand pathway may be involved in the pathophysiology of idiopathic pulmonary fibrosis (IPF), The aim of this study was to investig ate Fas-signalling molecules in epithelial cells in IPF, The immunohistochemistry for FADD and caspase-1 and -3 and terminal deoxynu cleotidyl transferase-mediated deoxyuridinetriphosphate nick endlabelling ( TUNEL) methods were performed in lung tissues from 10 patients with IPF obt ained by thoracoscopic biopsy and in seven normal lung parenchyma specimens . The induction of caspases expression and activation by Fas-ligation on lu ng epithelial cell line A549 was also investigated. The immunoreactivity grade for FADD and caspase-1 and -3, and positive sign als for TUNEL were significantly increased in epithelial cells of IPF compa red with controls. Fas-ligation induced upregulation of caspase-1 and -3 ex pression in the nucleus and cytoplasm in A549 cells. Procaspase-1, -3, and -8 were activated in apoptotic cells, but not in viable cells. Although direct measurement of the caspase activity in lung epithelial cell s of idiopathic pulmonary fibrosis could not be made, these results suggest that the Fas-signalling pathway is upregulated in lung epithelial cells of idiopathic pulmonary fibrosis.