Journal ArticleDOI
Function and activation of NF-kappa B in the immune system.
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TLDR
The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, severe phase response, and radiation damage.Abstract:
NF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling, and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins. In vertebrates, five distinct DNA binding subunits are currently known which might extensively heterodimerize, thereby forming complexes with distinct transcriptional activity, DNA sequence specificity, and cell type- and cell stage-specific distribution. The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates. I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes. An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus. Other I kappa B proteins are rather involved in terminating NF-kappa B's activity in the nucleus. The intracellular events that lead to the inactivation of I kappa B, i.e. the activation of NF-kappa B, are complex. They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells' redox status. Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, acute phase response, and radiation damage. The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes.read more
Citations
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Journal ArticleDOI
Overexpression of I Kappa B Alpha Without Inhibition of NF-κB Activity and Mutations in the I Kappa B Alpha Gene in Reed-Sternberg Cells
Florian Emmerich,Martina Meiser,Martina Meiser,Michael Hummel,Michael Hummel,Gudrun Demel,Gudrun Demel,Hans-Dieter Foss,Hans-Dieter Foss,Franziska Jundt,Franziska Jundt,Stephan Mathas,Stephan Mathas,Daniel Krappmann,Daniel Krappmann,Claus Scheidereit,Claus Scheidereit,Harald Stein,Harald Stein,Bernd Dörken,Bernd Dörken +20 more
TL;DR: It is suggested that the observed IkappaBalpha mutations contribute to constitutive NF-kappaB activity in cultured and primary HRS cells and are therefore involved in the pathogenesis of these Hodgkin's disease (HD) patients.
Journal ArticleDOI
Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer's disease.
Chia-Hsiung Chen,Weihui Zhou,Shengchun Liu,Yu Deng,Fang Cai,Masahide Tone,Yukiko Tone,Yigang Tong,Weihong Song +8 more
TL;DR: The study suggests that inhibition of NF-κB-mediated BACE1 expression may be a valuable drug target for AD therapy, and indicates that NSAIDs could block the inflammation-induced Bace1 transcription and Aβ production.
Journal ArticleDOI
A role of poly (ADP-ribose) polymerase in NF-kappaB transcriptional activation.
TL;DR: It is shown that poly (ADP ribose) polymerase (PARP) is required for specific NF-κB transcriptional activation in vivo and that PARP is an important cofactor in the activation cascade of NF-kkB-dependent target genes.
Journal ArticleDOI
Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms
TL;DR: It appears that significant portion of the chemopreventive effects of isothiocyanates may be associated with the inhibition of the metabolic activation of carcinogens by cytochrome P450s (Phase I), coupled with strong induction of Phase II detoxifying and cellular defensive enzymes.
Journal ArticleDOI
Immunosuppressant PG490 (Triptolide) Inhibits T-cell Interleukin-2 Expression at the Level of Purine-box/Nuclear Factor of Activated T-cells and NF-κB Transcriptional Activation
Daoming Qiu,Guohua Zhao,Yosuke Aoki,Lingfang Shi,Anne Uyei,Saman Nazarian,James C.-H. Ng,Peter N. Kao +7 more
TL;DR: PG490 (triptolide) is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties that inhibits interleukin(IL)-2 expression by normal human peripheral blood lymphocytes stimulated with phorbol 12-myristate 13-acetate and antibody to CD3.
References
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Book
Free radicals in biology and medicine
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Journal ArticleDOI
Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.
TL;DR: It is shown that micromolar concentrations of H2O2 can induce the expression and replication of HIV‐1 in a human T cell line and suggests that diverse agents thought to activate NF‐kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI.
Journal ArticleDOI
Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
Ranjan Sen,David Baltimore +1 more
TL;DR: In this paper, an electrophoretic mobility shift assay with end-labeled DNA fragments was used to characterize proteins that bind to the immunoglobulin (Ig) heavy chain and the kappa light chain enhancers.
Journal ArticleDOI
The mechanism of action of cyclosporin A and FK506
TL;DR: Recent findings that indicate CsA and FK506 operate as prodrugs are reviewed: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.
Journal ArticleDOI
An inducible transcription factor activates expression of human immunodeficiency virus in T cells
Gary J. Nabel,David Baltimore +1 more
TL;DR: Activation of T cells, which increases HIV expression up to 50-fold, correlated with induction of a DNA binding protein indistinguishable from a recognized transcription factor, called NF-κB, with binding sites in the viral enhancer.