Linked Life Data

18262272

Source:http://linkedlifedata.com/resource/pubmed/id/18262272

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-3-24
pubmed:abstractText
Cytokines interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are involved in acute phase response (APR). C-reactive protein (CRP), the prototype acute phase protein, may represent an important component in the pathogenesis of arteriosclerosis and may also be a target for drug development. Inhibition of CRP synthesis is one potential strategy. Understanding CRP synthesis, however, is a prerequirement for the development of CRP-inhibitors. From studies in hepatoma cell lines, IL-1beta and IL-6 were considered as equal inductors of APR and CRP. We investigated IL-1beta- and IL-6-effects on primary human hepatocytes (PHH) and Hep3B-cells. Kupffer cell contamination in PHH preparations was <3%. In PHH, several APP like CRP, haptoglobin (HP), lipopolysaccharide-binding protein (LBP) or hepcidin (HAMP) were regulated similarly by IL-1beta and IL-6, though signal transduction pathways of these cytokines are different. In Hep3B-cells, APP were regulated exclusively by IL-6. IL-1beta induced IL-6-synthesis in PHH but not in Hep3B-cells. C/EBPbeta-overexpression in Hep3B-cells reconstituted IL-1beta-mediated IL-6/CRP inducibility. In PHH and in C/EBPbeta-overexpressing Hep3B-cells, neutralizing anti-IL-6-antibodies blocked IL-1beta-mediated APR. Inhibition of protein synthesis and NFkappaB-signalling blocked IL-1beta- but not IL-6-mediated CRP-expression in PHH, whereas Janus-Kinase-1-inhibition blocked IL-1beta- and IL-6-mediated APR. IL-1beta induces APR in PHH via an NFkappaB- and C/EBPbeta-dependent autocrine IL-6-loop. These findings partly reconcile the understanding of APR and may help to design a transcriptional suppressor of CRP for the treatment of cardiovascular disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2678-89
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Interleukin-1beta stimulates acute phase response and C-reactive protein synthesis by inducing an NFkappaB- and C/EBPbeta-dependent autocrine interleukin-6 loop.
pubmed:affiliation
Sanofi Aventis Pharma GmbH, TD Cardiovascular, 65926 Frankfurt am Main, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't