Source:http://linkedlifedata.com/resource/pubmed/id/15879132
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2005-5-9
|
| pubmed:abstractText |
As sentinels of host defense, intestinal epithelial cells respond to the viral pathogen rotavirus by activating a gene expression that promotes immune cell recruitment and activation. We hypothesized that epithelial sensing of rotavirus might target dsRNA, which can be detected by TLR3 or protein kinase R (PKR). Accordingly, we observed that synthetic dsRNA, polyinosinic acid:cytidylic acid (poly(I:C)), potently induced gene remodeling in model intestinal epithelia with the specific pattern of expressed genes, including both classic proinflammatory genes (e.g., IL-8), as well as genes that are classically activated in virus-infected cells (e.g., IFN-responsive genes). Poly(I:C)-induced IL-8 was concentration dependent (2-100 mug/ml) and displayed slower kinetics compared with IL-8 induced by bacterial flagellin (ET(50) approximately 24 vs 8 h poly(I:C) vs flagellin, respectively). Although model epithelia expressed detectable TLR3 mRNA, neither TLR3-neutralizing Abs nor chloroquine, which blocks activation of intracellular TLR3, attenuated epithelial responses to poly(I:C). Conversely, poly(I:C)-induced phosphorylation of PKR and inhibitors of PKR, 2-aminopurine and adenine, ablated poly(I:C)-induced gene expression but had no effect on gene expression induced by flagellin, thus suggesting that intestinal epithelial cell detection of dsRNA relies on PKR. Consistent with poly(I:C) detection by an intracellular molecule such as PKR, we observed that both uptake of and responses to poly(I:C) were polarized to the basolateral side. Lastly, we observed that the pattern of pharmacologic inhibition of responses to poly(I:C) was identical to that seen in response to infection by live rotavirus, indicating a potentially important role for PKR in activating intestinal epithelial gene expression in rotavirus infection.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Flagellin,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Poly I-C,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Double-Stranded,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/TLR3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 3,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
174
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
6322-31
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:15879132-Adjuvants, Immunologic,
pubmed-meshheading:15879132-Cell Line,
pubmed-meshheading:15879132-Cytokines,
pubmed-meshheading:15879132-Flagellin,
pubmed-meshheading:15879132-Gene Expression Profiling,
pubmed-meshheading:15879132-Humans,
pubmed-meshheading:15879132-Inflammation Mediators,
pubmed-meshheading:15879132-Interleukin-8,
pubmed-meshheading:15879132-Intestinal Mucosa,
pubmed-meshheading:15879132-Intracellular Fluid,
pubmed-meshheading:15879132-Membrane Glycoproteins,
pubmed-meshheading:15879132-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:15879132-Poly I-C,
pubmed-meshheading:15879132-RNA, Double-Stranded,
pubmed-meshheading:15879132-RNA, Viral,
pubmed-meshheading:15879132-Receptors, Cell Surface,
pubmed-meshheading:15879132-Rotavirus,
pubmed-meshheading:15879132-Toll-Like Receptor 3,
pubmed-meshheading:15879132-Toll-Like Receptors,
pubmed-meshheading:15879132-Virus Activation,
pubmed-meshheading:15879132-eIF-2 Kinase
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Protein kinase R mediates intestinal epithelial gene remodeling in response to double-stranded RNA and live rotavirus.
|
| pubmed:affiliation |
Department of Pathology and Laboratory Medicine, Epithelial Pathobiology Unit, Emory University School of Medicine, Atlanta, GA 30322, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
|