1. Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species.
- Author
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Uchikura, Keiichiro, Wada, Tatehiko, Hoshino, Sumito, Nagakawa, Yuichi, Aiko, Takashi, Bulkley, Gregory B., Klein, Andrew S., and Sun, Zhaoh
- Subjects
LIGANDS (Biochemistry) ,KUPFFER cells ,REACTIVE oxygen species ,APOPTOSIS ,CELL death ,IMMUNOREGULATION - Abstract
Fas-Fas ligand (FasL)-dependent pathways exert a suppressive effect on inflammatory responses in immune-privileged organs. FasL expression in hepatic Kupffer cells (KC) has been implicated in hepatic immunoregulation. In this study, modulation of FasL expression of KC by endogenous gut-derived bacterial LPS and the role of reactive oxygen species (ROS) as potential mediators of FasL expression in KC were investigated. LPS stimulation of KC resulted in upstream ROS generation and, subsequently, increased FasL expression and consequent Jurkat cell (Fas-positive) apoptosis. The NADPH oxidase and xanthine oxidase enzymatic pathways appear to be major sources of this upstream ROS generation. Increased FasL expression was blocked by antioxidants and by enzymatic blocking of ROS generation. Exogenous administration of H
2 O2 stimulated KC FasL expression and subsequent Jurkat cell apoptosis. Intracellular endogenous ROS generation may therefore represent an important signal transduction pathway for FasL expression in KC. [ABSTRACT FROM AUTHOR]- Published
- 2004
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