Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species

Uchikura, Keiichiro; Wada, Tetsuji; Hoshino, Satoshi; Nagakawa, Yuichi; Aiko, Takashi; Bulkley, Gregory B.; Klein, Andrew S.; Sun, Zhaoli

doi:10.1152/ajpgi.00314.2003

Cited by 52 publications

(44 citation statements)

References 38 publications

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“…They have been suggested to play an important role in clearing pathogens derived from the gut (500). They are also involved in the regulation of gene expression, particularly the expression of the CD95 ligand (890) and NFB-dependent production of TNF-␣ (753). Finally, they have been suggested to be essential mediators in antigen presentation by Kupffer cells (568).…”

Section: Livermentioning

confidence: 99%

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Bedard¹,

Krause²

2007

Physiological Reviews

5,934

117

5,778

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For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91phox), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX actvity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.

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Section: Livermentioning

confidence: 99%

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Bedard¹,

Krause²

2007

Physiological Reviews

5,934

117

5,778

View full text Add to dashboard Cite

show abstract

“…In the extrinsic pathway of apoptosis, ROS are generated by Fas ligand as an upstream event for Fas activation. In turn, ROS are required for Fas phosphorylation at the tyrosine residue, which is a signal for subsequent recruitment of Fas-associated protein with death domain and caspase 8 and for apoptosis induction (72,216,257,305). In addition, ROS are required for the ubiquitination and subsequent degradation of the FLICE inhibitory protein to further enhance Fas activation (322).…”

Section: Fig 2 Major Sources Of Ros Inside a Cancer Cellmentioning

confidence: 99%

Upsides and Downsides of Reactive Oxygen Species for Cancer: The Roles of Reactive Oxygen Species in Tumorigenesis, Prevention, and Therapy

Gupta

Hevia

Patchva

et al. 2012

Antioxidants & Redox Signaling

632

464

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Significance: Extensive research during the last quarter century has revealed that reactive oxygen species (ROS) produced in the body, primarily by the mitochondria, play a major role in various cell-signaling pathways. Most risk factors associated with chronic diseases (e.g., cancer), such as stress, tobacco, environmental pollutants, radiation, viral infection, diet, and bacterial infection, interact with cells through the generation of ROS. Recent Advances: ROS, in turn, activate various transcription factors (e.g., nuclear factor kappa-light-chain-enhancer of activated B cells [NF-jB], activator protein-1, hypoxia-inducible factor-1a, and signal transducer and activator of transcription 3), resulting in the expression of proteins that control inflammation, cellular transformation, tumor cell survival, tumor cell proliferation and invasion, angiogenesis, and metastasis. Paradoxically, ROS also control the expression of various tumor suppressor genes (p53, Rb, and PTEN). Similarly, c-radiation and various chemotherapeutic agents used to treat cancer mediate their effects through the production of ROS. Interestingly, ROS have also been implicated in the chemopreventive and anti-tumor action of nutraceuticals derived from fruits, vegetables, spices, and other natural products used in traditional medicine. Critical Issues: These statements suggest both ''upside'' (cancer-suppressing) and ''downside'' (cancer-promoting) actions of the ROS. Thus, similar to tumor necrosis factor-a, inflammation, and NF-jB, ROS act as a double-edged sword. This paradox provides a great challenge for researchers whose aim is to exploit ROS stress for the development of cancer therapies. Future Directions: The various mechanisms by which ROS mediate paradoxical effects are discussed in this article. The outstanding questions and future directions raised by our current understanding are discussed. Antioxid. Redox Signal. 16, 1295Signal. 16, -1322

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“…It has been reported that the administration of TA activates NF-B followed by the generation of ROS in the liver (Lu et al, 1999), and it was also reported that LPS treatment increases the generation of ROS in Kupffer cells (Uchikura et al, 2004) and the NF-B binding activity in hepatocytes (Freedman et al, 1992). Reactive oxygen species contribute to the pathogenesis of a variety of liver diseases, such as acetaminophen overdose, hemochromatosis, alcoholic liver injury, toxin exposure, and viral hepatitis (Slater, 1984).…”

Section: Luminescence-based Analysis Of Nf-b Activation 449mentioning

confidence: 99%

“…In the LPS/ GalN-induced fulminant hepatitis model, Man-or Suc-catalase also effectively inhibited NF-B activation and liver injury. Because LPS is mainly recognized by the toll-like receptor 4 expressed on Kupffer cells (Su et al, 2000) and subsequently produce ROS (Uchikura et al, 2004) and inflammatory cytokines (Su et al, 2000), the delivery of catalase to the nonparenchymal cells is efficient. The cause of TAor LPS/GalN-induced death is reported to be ROS-mediated liver dysfunction (Okuyama et al, 2003).…”

Section: Downloaded Frommentioning

confidence: 99%

Analysis of In Vivo Nuclear Factor-κB Activation during Liver Inflammation in Mice: Prevention by Catalase Delivery

Hyoudou¹,

Nishikawa²,

Kobayashi³

et al. 2006

Mol Pharmacol

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Nuclear factor-B (NF-B) is a transcription factor that plays crucial roles in inflammation, immunity, cell proliferation, and apoptosis. Until now, there have been few studies of NF-B activation in whole animals because of experimental difficulties. Here, we show that mice receiving a simple injection of plasmid vectors can be used to examine NF-B activation in the liver. Two plasmid vectors, pNF-B-Luc (firefly luciferase gene) and pRL-SV40 (Renilla reniformis luciferase gene), were injected into the tail vein of mice by the hydrodynamics-based procedure, an established method of gene transfer to mouse liver. Then, the ratio of the firefly and R. reniformis luciferase activities (F/R) was used as an indicator of the NF-B activity in the liver. Injection of thioacetamide or lipopolysaccharide plus D-galactosamine increased the F/R ratio in the liver, and this was significantly (P Ͻ 0.001) inhibited by an intravenous injection of catalase derivatives targeting liver nonparenchymal cells. Imaging the firefly luciferase expression in live mice clearly demonstrated that the catalase derivatives efficiently prevented the NF-B-mediated expression of the firefly luciferase gene. Plasma transaminases and the survival rate of mice supported the findings obtained by the luminescence-based analyses. Thus, this method, which requires no genetic recombination techniques, is highly sensitive to the activation of NF-B and allows us to continuously examine the activation in live animals. In conclusion, this novel, simple, and sensitive method can be used not only for analyzing the NF-B activation in the organ under different inflammatory conditions but also for screening drug candidates for the prevention of liver inflammation.

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Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species

Cited by 52 publications

References 38 publications

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

Upsides and Downsides of Reactive Oxygen Species for Cancer: The Roles of Reactive Oxygen Species in Tumorigenesis, Prevention, and Therapy

Analysis of In Vivo Nuclear Factor-κB Activation during Liver Inflammation in Mice: Prevention by Catalase Delivery

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