Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species
Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species
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DOI：
10.1152/ajpgi.00314.2003
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发表时间：
2004-09-01
影响因子：
4.5
通讯作者：
Sun, ZL
中科院分区：
文献类型：
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作者：
Uchikura, K;Wada, T;Sun, ZL
Fas-Fas配体(Fas-Fas Ligand，FasL)依赖的途径对免疫特免性器官的炎症反应具有抑制作用。肝脏枯否细胞(KC)中FasL的表达与肝脏免疫调节有关。本研究探讨内源性细菌脂多糖对KC细胞FasL表达的调节作用，以及活性氧(ROS)在KC细胞FasL表达中的作用。内毒素对KC的刺激导致上游ROS的产生，继而增加FasL的表达，从而导致Jurkat细胞(Fas阳性)的凋亡。NADPH氧化酶和黄嘌呤氧化酶的酶途径似乎是上游ROS产生的主要来源。增加的FasL表达可被抗氧化剂和酶抑制ROS的生成所阻断。外源性H_2O_2刺激KC-FasL表达，进而诱导Jurkat细胞凋亡。因此，细胞内源性ROS的产生可能是KC中FasL表达的重要信号转导途径。
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 H2O2 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.