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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Steroid Hormone Regulation of Cytokine Secretion by Proteolipid Protein-Specific CD4 1 T Cell Clones Isolated from Multiple Sclerosis Patients and Normal Control Subjects 1
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Extracellular signal–regulated protein kinase signaling pathway negatively regulates the phenotypic and functional maturation of monocyte-derived human dendritic cells
Amaya Puig-Kröger,Miguel Relloso,Oskar Fernández-Capetillo,Ana M. Zubiaga,Augusto Silva,Carmelo Bernabeu,Angel L. Corbí +6 more
TL;DR: The results indicate that the ERK and p38 MAPK signaling pathways differentially regulate maturation of MDDC and suggest that their relative levels of activation might modulate the initial commitment of naive T-helper cells toward Th1 or Th2 subsets.
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Induction of Apoptosis by Double-Stranded-RNA-Dependent Protein Kinase (PKR) Involves the α Subunit of Eukaryotic Translation Initiation Factor 2 and NF-κB
TL;DR: These findings provide direct evidence for the involvement of eIF-2α and NF-κB in the induction of apoptosis by PKR and treatment with two different proteasome inhibitors prevented PKR-induced apoptosis.
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Inflammatory Responses in Brain Ischemia
TL;DR: Recent advances in neuroinflammation and the modulation of inflammatory signaling pathways in brain ischemia are reviewed and potential targets for treatment of ischemic stroke are covered.
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Different mechanisms control signal-induced degradation and basal turnover of the NF-kappaB inhibitor IkappaB alpha in vivo.
TL;DR: It is shown that tumor necrosis factor alpha (TNFalpha) induced breakdown of IkappaB alpha but not its basal turnover coincides with ubiquitination in the amino‐terminal signal response domain (SRD), important for understanding alternative modes of controlling NF‐kappaB activity.
References
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Book
Free radicals in biology and medicine
TL;DR: 1. Oxygen is a toxic gas - an introduction to oxygen toxicity and reactive species, and the chemistry of free radicals and related 'reactive species'
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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.
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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.