Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1999-5-6
pubmed:abstractText
To continue our investigation of the cellular events that occur following human CMV (HCMV) infection, we focused on the regulation of cellular activation following viral binding to human monocytes. First, we showed that viral binding induced a number of immunoregulatory genes (IL-1beta, A20, NF-kappaB-p105/p50, and IkappaBalpha) in unactivated monocytes and that neutralizing Abs to the major HCMV glycoproteins, gB (UL55) and gH (UL75), inhibited the induction of these genes. Next, we demonstrated that these viral ligands directly up-regulated monocyte gene expression upon their binding to their appropriate cellular receptors. We then investigated if HCMV binding also resulted in the translation and secretion of cytokines. Our results showed that HCMV binding to monocytes resulted in the production and release of IL-1beta protein. Because these induced gene products have NF-kappaB sites in their promoter regions, we next examined whether there was an up-regulation of nuclear NF-kappaB levels. These experiments showed that, in fact, NF-kappaB was translocated to the nucleus following viral binding or purified viral ligand binding. Changes in IkappaBalpha levels correlated with the changes in NF-kappaB translocation. Lastly, we demonstrated that p38 kinase activity played a central role in IL-1beta production and that it was rapidly up-regulated following infection. These results support our hypothesis that HCMV initiates a signal transduction pathway that leads to monocyte activation and pinpoints a potential mechanism whereby HCMV infection of monocytes can result in profound pathogenesis, especially in chronic inflammatory-type conditions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Anti-Idiotypic, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Viral, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Virus, http://linkedlifedata.com/resource/pubmed/chemical/Viral Envelope Proteins, http://linkedlifedata.com/resource/pubmed/chemical/glycoprotein B, Simplexvirus, http://linkedlifedata.com/resource/pubmed/chemical/glycoprotein H, Cytomegalovirus, http://linkedlifedata.com/resource/pubmed/chemical/glycoprotein H, Human..., http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4806-16
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10202024-Antibodies, Anti-Idiotypic, pubmed-meshheading:10202024-Antibodies, Viral, pubmed-meshheading:10202024-Binding Sites, pubmed-meshheading:10202024-Binding Sites, Antibody, pubmed-meshheading:10202024-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10202024-Cells, Cultured, pubmed-meshheading:10202024-Cytomegalovirus, pubmed-meshheading:10202024-DNA-Binding Proteins, pubmed-meshheading:10202024-Enzyme Induction, pubmed-meshheading:10202024-Gene Expression Regulation, Viral, pubmed-meshheading:10202024-Humans, pubmed-meshheading:10202024-I-kappa B Proteins, pubmed-meshheading:10202024-Interleukin-1, pubmed-meshheading:10202024-Macrophage Activation, pubmed-meshheading:10202024-Mitogen-Activated Protein Kinases, pubmed-meshheading:10202024-Monocytes, pubmed-meshheading:10202024-NF-kappa B, pubmed-meshheading:10202024-Neutralization Tests, pubmed-meshheading:10202024-Phosphorylation, pubmed-meshheading:10202024-RNA, Messenger, pubmed-meshheading:10202024-Receptors, Virus, pubmed-meshheading:10202024-Up-Regulation, pubmed-meshheading:10202024-Viral Envelope Proteins, pubmed-meshheading:10202024-p38 Mitogen-Activated Protein Kinases
pubmed:year
1999
pubmed:articleTitle
Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression.
pubmed:affiliation
Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina, Chapel Hill 27599, USA. yurochko@med.unc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.