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rdf:type |
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lifeskim:mentions |
umls-concept:C0021753,
umls-concept:C0026473,
umls-concept:C0030012,
umls-concept:C0035820,
umls-concept:C0037083,
umls-concept:C0086418,
umls-concept:C0439831,
umls-concept:C1418215,
umls-concept:C1554080,
umls-concept:C1706198,
umls-concept:C1709694,
umls-concept:C1710082
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pubmed:issue |
12
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pubmed:dateCreated |
2008-6-4
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pubmed:abstractText |
P2X(7) receptors (P2X(7)Rs) are ATP-gated ion channels that trigger caspase-1 activation in the presence of TLR ligands. Inflammatory caspase-1 is responsible for the proteolytic activation of IL-1beta. However, the signaling events that couple P2X(7)Rs to caspase-1 activation remain undefined. In this study we demonstrate that ATP-induced cellular oxidation is critical for caspase-1 activation and subsequent IL-1beta processing. Purinergic receptor stimulation, including P2X(7)Rs, of endotoxin-primed human monocytes augments NADPH oxidase activity whereas concurrent purinergic receptor stimulation triggers protein denitroyslation, leading to the formation of peroxynitrite. IL-1beta cleavage is blocked under conditions where superoxide anion formation is blocked or monocytes are treated with antioxidants or a peroxynitrite scavenger. Nigericin, a K(+)/H(+) antiporter, also increases NADPH oxidase activity, leading to IL-1beta and caspase-1 processing that is blocked by a peroxynitrite scavenger or inhibition of NADPH oxidase. These data demonstrate that signaling via NADPH oxidase activity is fundamental for the processing of mature IL-1beta induced by P2X(7)R stimulation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/P2RX7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2X7,
http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosothiols
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
180
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8410-20
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18523309-Adenosine Triphosphate,
pubmed-meshheading:18523309-Caspase 1,
pubmed-meshheading:18523309-Cell Line, Tumor,
pubmed-meshheading:18523309-Enzyme Activation,
pubmed-meshheading:18523309-Extracellular Fluid,
pubmed-meshheading:18523309-Humans,
pubmed-meshheading:18523309-Interleukin-1beta,
pubmed-meshheading:18523309-Ion Channel Gating,
pubmed-meshheading:18523309-Monocytes,
pubmed-meshheading:18523309-NADPH Oxidase,
pubmed-meshheading:18523309-Nitric Oxide,
pubmed-meshheading:18523309-Oxidants,
pubmed-meshheading:18523309-Oxidation-Reduction,
pubmed-meshheading:18523309-Protein Processing, Post-Translational,
pubmed-meshheading:18523309-Receptors, Purinergic P2,
pubmed-meshheading:18523309-Receptors, Purinergic P2X7,
pubmed-meshheading:18523309-S-Nitrosothiols,
pubmed-meshheading:18523309-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
A key role for redox signaling in rapid P2X7 receptor-induced IL-1 beta processing in human monocytes.
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pubmed:affiliation |
Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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