Source:http://linkedlifedata.com/resource/pubmed/id/18490713
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
|
| pubmed:dateCreated |
2008-5-20
|
| pubmed:abstractText |
The proinflammatory IL-1 cytokines IL-1alpha, IL-1beta, and IL-18 are key mediators of the acute immune response to injury and infection. Mechanisms underlying their cellular release remain unclear. Activation of purinergic P2X(7) receptors (P2X(7)R) by extracellular ATP is a key physiological inducer of rapid IL-1beta release from LPS-primed macrophage. We investigated patterns of ATP-mediated release of IL-1 cytokines from three macrophage types in attempts to provide direct evidence for or against distinct release mechanisms. We used peritoneal macrophage from P2X(7)R(-/-) mice and found that release of IL-1alpha, IL-18, as well as IL-1beta, by ATP resulted exclusively from activation of P2X(7)R, release of all these IL-1 cytokines involved pannexin-1 (panx1), and that there was both a panx1-dependent and -independent component to IL-1beta release. We compared IL-1-release patterns from LPS-primed peritoneal macrophage, RAW264.7 macrophage, and J774A.1 macrophage. We found RAW264.7 macrophage readily release pro-IL-1beta independently of panx1 but do not release mature IL-1beta because they do not express apoptotic speck-like protein with a caspase-activating recruiting domain and so have no caspase-1 inflammasome activity. We delineated two distinct release pathways: the well-known caspase-1 cascade mediating release of processed IL-1beta that was selectively blocked by inhibition of caspase-1 or panx1, and a calcium-independent, caspase-1/panx1-independent release of pro-IL-1beta that was selectively blocked by glycine. None of these release responses were associated with cell damage or cytolytic effects. This provides the first direct demonstration of a distinct signaling mechanism responsible for ATP-induced release of pro-IL-1beta.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Connexins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P2rx7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Panx1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pycard protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2X7
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
180
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
7147-57
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:18490713-Adenosine Triphosphate,
pubmed-meshheading:18490713-Animals,
pubmed-meshheading:18490713-Caspase 1,
pubmed-meshheading:18490713-Cell Death,
pubmed-meshheading:18490713-Cell Line,
pubmed-meshheading:18490713-Connexins,
pubmed-meshheading:18490713-Cytoskeletal Proteins,
pubmed-meshheading:18490713-Interleukin-18,
pubmed-meshheading:18490713-Interleukin-1alpha,
pubmed-meshheading:18490713-Interleukin-1beta,
pubmed-meshheading:18490713-Lipopolysaccharides,
pubmed-meshheading:18490713-Macrophages,
pubmed-meshheading:18490713-Male,
pubmed-meshheading:18490713-Mice,
pubmed-meshheading:18490713-Mice, Inbred BALB C,
pubmed-meshheading:18490713-Mice, Inbred C57BL,
pubmed-meshheading:18490713-Mice, Knockout,
pubmed-meshheading:18490713-Nerve Tissue Proteins,
pubmed-meshheading:18490713-Receptors, Purinergic P2,
pubmed-meshheading:18490713-Receptors, Purinergic P2X7
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage.
|
| pubmed:affiliation |
Faculty of Life Science, University of Manchester, Manchester, United Kingdom.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|