title: Induction of interleukin-8 secretion and apoptosis in bronchiolar epithelial cells by Fas ligation.
abstract: Epithelial cell injury is the common manifestation of lung injury. Contributing to such injury of epithelial cells is apoptosis. Although apoptosis is part of the normal process of epithelial renewal, in excess it is pathologic. We previously demonstrated the excessive apoptosis of lung epithelial cells and the upregulation of Fas and Fas ligand (FasL) in fibrosing lung diseases. We also showed that inhalation of anti-Fas antibody induced lung injury and fibrosis in mice. Interleukin (IL)-8 is one of the most important cytokines in the pathophysiology of acute lung injury and pulmonary fibrosis. In this study we investigated whether Fas ligation induces IL-8 secretion in addition to apoptosis in bronchiolar epithelial cells in vitro. Bronchiolar epithelial cells underwent apoptosis and also secreted IL-8 in response to tumor necrosis factor (TNF)-alpha or Fas ligation. New gene expression and protein synthesis were not necessary for Fas ligation- and TNF-alpha- mediated apoptosis, but were necessary for IL-8 secretion. We further found that Fas ligation induced activation of nuclear factor-kappa B. We conclude that the Fas/FasL pathway not only mediates apoptosis but also plays a proinflammatory role, and that stimulation of the Fas/FasL pathway in bronchiolar epithelial cells leads to IL-8 production, which may amplify the inflammatory cascade in lung injury and pulmonary fibrosis.
authors.affiliation: Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan. hagi@mailserver.med.kyushu-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Hagimoto
authors.forename: K
authors.initials: K
authors.lastname: Kuwano
authors.forename: M
authors.initials: M
authors.lastname: Kawasaki
authors.forename: M
authors.initials: M
authors.lastname: Yoshimi
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: R
authors.initials: R
authors.lastname: Kunitake
authors.forename: T
authors.initials: T
authors.lastname: Maeyama
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Hara
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008854:Microscopy, Electron; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D003609:Dactinomycin; D007371:Interferon-gamma; D003513:Cycloheximide