Source:http://linkedlifedata.com/resource/pubmed/id/12468547
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
2003-2-10
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pubmed:abstractText |
It is well established that cytokines can induce the production of chemokines, but the role of chemokines in the regulation of cytokine expression has not been fully investigated. Exposure of rat cardiac-derived endothelial cells (CDEC) to lipopolysaccharide-induced CXC chemokine (LIX), and to a lesser extent to KC and MIP-2, activated NF-kappaB and induced kappaB-driven promoter activity. LIX did not activate Oct-1. LIX-induced interleukin-1beta and tumor necrosis factor-alpha promoter activity, and up-regulated mRNA expression. Increased transcription and mRNA stability both contributed to cytokine expression. LIX-mediated cytokine gene transcription was inhibited by interleukin-10. Transient overexpression of kinase-deficient NF-kappaB-inducing kinase (NIK) and IkappaB kinase (IKK), and dominant negative IkappaB significantly inhibited LIX-mediated NF-kappaB activation in rat CDEC. Inhibition of G(i) protein-coupled signal transduction, poly(ADP-ribose) polymerase, phosphatidylinositol 3-kinase, and the 26 S proteasome significantly inhibited LIX-mediated NF-kappaB activation and cytokine gene transcription. Blocking CXCR2 attenuated LIX-mediated kappaB activation and kappaB-driven promoter activity in rat CDEC that express both CXCR1 and -2, and abrogated its activation in mouse CDEC that express only CXCR2. These results indicate that LIX activates NF-kappaB and induces kappaB-responsive proinflammatory cytokines via either CXCR1 or CXCR2, and involved phosphatidylinositol 3-kinase, NIK, IKK, and IkappaB. Thus, in addition to attracting and activating neutrophils, the ELR(+) CXC chemokines amplify the inflammatory cascade, stimulating local production of cytokines that have negative inotropic and proapoptotic effects.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL1,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/Chemotactic Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cxcl5 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-8A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-8B
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4675-86
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12468547-Animals,
pubmed-meshheading:12468547-Cells, Cultured,
pubmed-meshheading:12468547-Chemokine CXCL1,
pubmed-meshheading:12468547-Chemokine CXCL2,
pubmed-meshheading:12468547-Chemokine CXCL5,
pubmed-meshheading:12468547-Chemokines,
pubmed-meshheading:12468547-Chemokines, CXC,
pubmed-meshheading:12468547-Chemotactic Factors,
pubmed-meshheading:12468547-Endothelium,
pubmed-meshheading:12468547-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12468547-Mice,
pubmed-meshheading:12468547-NF-kappa B,
pubmed-meshheading:12468547-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12468547-Rats,
pubmed-meshheading:12468547-Receptor Cross-Talk,
pubmed-meshheading:12468547-Receptors, Interleukin-8A,
pubmed-meshheading:12468547-Receptors, Interleukin-8B,
pubmed-meshheading:12468547-Signal Transduction
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pubmed:year |
2003
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pubmed:articleTitle |
Chemokine-cytokine cross-talk. The ELR+ CXC chemokine LIX (CXCL5) amplifies a proinflammatory cytokine response via a phosphatidylinositol 3-kinase-NF-kappa B pathway.
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pubmed:affiliation |
Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. chandraseka@uthscsa.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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