Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-2-10
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4675-86
pubmed:dateRevised
2010-11-18
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
pubmed:year
2003
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.
pubmed:affiliation
Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA. chandraseka@uthscsa.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't