RRC ID 41667
Author Tanaka T, Yoshimi M, Maeyama T, Hagimoto N, Kuwano K, Hara N.
Title Resistance to Fas-mediated apoptosis in human lung fibroblast.
Journal Eur. Respir. J.
Abstract The current authors have demonstrated previously that epithelial cell apoptosis, induced by the Fas-Fas ligand pathway, might be involved in fibrosing lung diseases. Whereas lung epithelial cells are sensitive to the Fas-mediated apoptosis, lung fibroblasts may be resistant to Fas-mediated apoptosis and replace damaged epithelial cells. The WI-38 lung fibroblast cell line and primary lung fibroblasts were used to examine the resistant to Fas-mediated apoptosis and the association of anti-apoptotic proteins with this resistance. The administration of agonistic anti-Fas antibody (CH-11) or cycloheximide alone did not induce apoptosis, whereas the co-administration of CH-11 with cycloheximide induced apoptosis in WI-38 cells, in which caspase-8 and -3, but not -9, were activated, and X chromosome-linked inhibitor of apoptosis (ILP) and FLICE-like inhibitor protein (FLIP(L)), but not bcl-xL and bcl-2, were remarkably down regulated. Primary lung fibroblasts were also resistant to Fas-mediated apoptosis, and ILP and FLIP appeared to be involved in this resistance. Furthermore, the results of immunohistochemistry demonstrated that fibroblasts expressed ILP and FLIP(L) proteins in lung tissues from patients with idiopathic pulmonary fibrosis. These results suggest that anti-apoptotic proteins such as X chromosome-linked inhibitor of apoptosis and FLICE-like inhibitor protein may play an important role in preventing Fas-mediated apoptosis in lung fibroblasts, and participate in the development of pulmonary fibrosis.
Volume 20(2)
Pages 359-68
Published 2002-8
DOI 10.1183/09031936.02.00252602
PMID 12212968
MeSH Adult Aged Apoptosis / drug effects* Apoptosis / physiology* CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins / analysis Cell Cycle / drug effects Cell Cycle / physiology Cell Line / drug effects Cell Line / pathology Cell Line / physiology Enzyme Inhibitors / analysis Fibroblasts / drug effects* Fibroblasts / pathology Fibroblasts / physiology* Humans In Vitro Techniques Inhibitor of Apoptosis Proteins Intracellular Signaling Peptides and Proteins* Lung / drug effects* Lung / pathology Lung / physiopathology* Middle Aged Proteins / analysis Pulmonary Fibrosis / pathology Pulmonary Fibrosis / physiopathology* fas Receptor / analysis* fas Receptor / pharmacology*
IF 11.807
Times Cited 66
Human and Animal Cells