Linked Life Data

16293680

Source:http://linkedlifedata.com/resource/pubmed/id/16293680

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-3-15
pubmed:abstractText
Bacterial DNA containing unmethylated cytosine-phosphate-guanosine motif (CpG-DNA) has been identified as a pathogen-associated molecular pattern, which is recognized by Toll-like receptors and activates immune cells to produce cytokines. The aim of the study was to characterize the ability of CpG-DNA to induce fever in mice. Intravenous administration of unmethylated CpG-DNA 1826 triggered an elevation of body temperature (T(b)) lasting several hours. The magnitude of T(b) elevation increased with an increase of dose of the oligonucleotide (administered in a range from 0.01 mg/kg to 1.0 mg/kg). A fever-like increase of T(b) in mice was partially dependent on IL-6, as IL-6 deficient mice responded with reduced fever to the CpG-DNA 1826. Meloxicam and sulindac sulfide, inhibitors of cyclooxygenases, reduced fever in mice challenged with CpG-DNA 1826, indicating that the process may also depend on prostaglandins. In fact, plasma levels of prostaglandin E(2), as well as IL-6, increased at 4 h postinjection of CpG-DNA 1826 into mice. These data demonstrate that the pathophysiological mechanism of the increase of T(b) induced by CpG-DNA 1826 is similar to fever induced by LPS. Both LPS and CpG-DNA 1826 failed to produce elevation of T(b) in mice deficient for a nuclear factor-kappaB (NF-kappaB) gene, further supporting the hypothesis that the two pyrogens provoke fever, using the same components of the cellular signaling metabolism. However, parthenolide, an inhibitor of I-kappaB kinase reduced fever due to CpG-DNA 1826, and did not affect fever to LPS, suggesting that the two structurally dissimilar pyrogens may affect different intracellular pathways leading to the upregulation of NF-kappaB. In support of this hypothesis, we demonstrate that C3H/HeJ mice, known to exhibit a mutation in the Toll-like receptor-4 gene, do not respond with fever to LPS. They respond, however, with fever after injection of CpG-DNA 1826. We conclude that bacterial DNA shares with components of the bacterial wall the capacity to elicit fever and may, consequently, be part of a novel class of exogenous pyrogens.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0363-6119
pubmed:author
pubmed:issnType
Print
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R871-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16293680-Animals, pubmed-meshheading:16293680-CpG Islands, pubmed-meshheading:16293680-DNA, pubmed-meshheading:16293680-Dinoprostone, pubmed-meshheading:16293680-Fever, pubmed-meshheading:16293680-Interleukin-6, pubmed-meshheading:16293680-Lipopolysaccharides, pubmed-meshheading:16293680-Male, pubmed-meshheading:16293680-Mice, pubmed-meshheading:16293680-Mice, Inbred C3H, pubmed-meshheading:16293680-Mice, Inbred C57BL, pubmed-meshheading:16293680-Mice, Knockout, pubmed-meshheading:16293680-Mice, Transgenic, pubmed-meshheading:16293680-NF-kappa B, pubmed-meshheading:16293680-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:16293680-Pyrogens, pubmed-meshheading:16293680-Sesquiterpenes, pubmed-meshheading:16293680-Signal Transduction, pubmed-meshheading:16293680-Temperature, pubmed-meshheading:16293680-Toll-Like Receptors
pubmed:year
2006
pubmed:articleTitle
Pyrogenicity of CpG-DNA in mice: role of interleukin-6, cyclooxygenases, and nuclear factor-kappaB.
pubmed:affiliation
Department of Immunology, Institute of General and Molecular Biology, Faculty of Biology and Earth Sciences, Nicolaus Copernicus University, 9 Gagarina St., 87-100 Torun, Poland. wkozak@biol.uni.torun.pl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural