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-associating protein with death domain (FADD) interacts with Fas and initiates apoptosis through activating caspase-8. It has previously been demonstrated that the Fas-Fas ligand pathway may be involved in the pathophysiology of idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate Fas-signalling molecules in epithelial cells in IPF. The immunohistochemistry for FADD and caspase-1 and -3 and terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick endlabelling (TUNEL) methods were performed in lung tissues from 10 patients with IPF obtained by thoracoscopic biopsy and in seven normal lung parenchyma specimens. The induction of caspases expression and activation by Fas-ligation on lung epithelial cell line A549 was also investigated. The immunoreactivity grade for FADD and caspase-1 and -3, and positive signals for TUNEL were significantly increased in epithelial cells of IPF compared with controls. Fas-ligation induced upregulation of caspase-1 and -3 expression 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 cells 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.
Maeyama
T
T
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kuwano
K
K
Kawasaki
M
M
Kunitake
R
R
Hagimoto
N
N
Matsuba
T
T
Yoshimi
M
M
Inoshima
I
I
Yoshida
K
K
Hara
N
N
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis*; D020170:Caspase 1 / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1