Linked Life Data

16179587

Source:http://linkedlifedata.com/resource/pubmed/id/16179587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-10-28
pubmed:abstractText
Apolipoprotein E (apoE) is synthesized in the liver and in macrophages, and it has antiatherogenic properties that are mediated, at least in part, through the regulation of plasma cholesterol homeostasis. Previous data suggest that apoE also has antiinflammatory properties that may contribute to protection against atherosclerosis independent of its role in lipid metabolism. In this study, apoE knockout and C57BL/6 mice were stimulated with low-dose lipopolysaccharide (LPS) and other Toll-like receptor (TLR) agonists. We show that apoE modulates the systemic type I inflammatory response in vivo. The proinflammatory cytokines tumor necrosis factor alpha, interleukin (IL)-6, IL-12, and interferon-gamma were upregulated to a significantly greater extent in apoE-deficient mice than in wild-type mice at both the mRNA and protein levels following administration of LPS. In contrast, hypercholesterolemic low-density lipoprotein receptor/apobec-1 double knockout mice had a similar cytokine response as wild-type mice, eliminating hypercholesterolemia as a cause for the exaggerated cytokine response. Importantly, reconstitution of apoE expression in the liver of apoE-deficient mice normalized the LPS-induced plasma protein levels of IL-12p40. Furthermore, there was selective upregulation of plasma IL-12 in apoE knockout mice by a TLR3 agonist, poly I:C, but not by other TLR agonists, CpG oligonucleotide or Toxoplasma gondii antigen. This implies that apoE selectively regulates TLR4- and TLR3-mediated signaling of IL-12 production. These results indicate that apoE modulates the T helper-1-type immune response in vivo by modulating IL-12 production.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
922-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Apolipoprotein E suppresses the type I inflammatory response in vivo.
pubmed:affiliation
Institute for Translational Medicine and Therapeutics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural