Linked Life Data

20458283

Source:http://linkedlifedata.com/resource/pubmed/id/20458283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-8-30
pubmed:abstractText
The source of circulating erythropoietin (EPO), the mediators and the mechanisms involved in the upregulation of EPO gene expression during acute-phase reaction are still poorly understood. Acute-phase reaction was induced by either intramuscular turpentine oil (TO) or intraperitoneal lipopolysaccharide (LPS) administration into wild-type and interleukin (IL)-6 knockout (KO) mice. Animals were killed at different time points and blood, liver and muscle tissue were collected. Serum levels of EPO were measured by enzyme-linked immunoadsorbent assay; liver and injured muscle samples were processed for RNA isolation and for protein analysis. EPO, hypoxia-inducible factors 1alpha and 2alpha (HIF-1alpha and HIF-2alpha) mRNA were analyzed by RT-PCR and the protein levels were analyzed by western blot and electrophoretic mobility shift assay. HIF-1alpha and HIF-2alpha localization was performed through immunofluorescence staining. EPO, HIF-1 and HIF-2 gene and protein expression levels were also analyzed in isolated mouse hepatocytes after stimulation with IL-6. In the wild-type animals, EPO serum levels increased dramatically at 12 h after the insults together with the hepatic gene expression. In TO-treated animals, the EPO gene expression reached an 8.2-fold increase at 12 h, and in LPS-treated mice a similar induction was recorded at 6 h (about 4.5-fold increase). In the IL-6KO strain, the upregulation after the inflammatory stimuli was much lower (only 2.0-fold increase). A progressive upregulation of HIF-1alpha and HIF-2alpha was detectable until 6 h after the insults, but only HIF-1alpha upregulation was reduced in IL-6KO mice. In isolated hepatocytes, stimulation with a single dose of IL-6 induced a nuclear accumulation of HIF-1alpha, in parallel with an increase of EPO mRNA. No effect on HIF-2alpha expression was found. IL-6 appears to be the main regulator of EPO gene expression and a major contributor for HIF-1alpha induction in hepatocytes and Kupffer cells during acute-phase response. The increase of HIF-2alpha, predominantly expressed in endothelial cells and fibroblast-like cells, seems not to be affected by the lack of IL-6.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1530-0307
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1306-24
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20458283-Acute-Phase Reaction, pubmed-meshheading:20458283-Animals, pubmed-meshheading:20458283-Anoxia, pubmed-meshheading:20458283-Enzyme Assays, pubmed-meshheading:20458283-Erythropoietin, pubmed-meshheading:20458283-Gene Expression, pubmed-meshheading:20458283-Genes, pubmed-meshheading:20458283-Hepatocytes, pubmed-meshheading:20458283-Hypoxia-Inducible Factor 1, pubmed-meshheading:20458283-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:20458283-Interleukin-6, pubmed-meshheading:20458283-Kupffer Cells, pubmed-meshheading:20458283-Liver, pubmed-meshheading:20458283-Male, pubmed-meshheading:20458283-Mice, pubmed-meshheading:20458283-Mice, Inbred C57BL, pubmed-meshheading:20458283-Mice, Knockout, pubmed-meshheading:20458283-RNA, Messenger, pubmed-meshheading:20458283-Recombinant Proteins, pubmed-meshheading:20458283-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20458283-Turpentine, pubmed-meshheading:20458283-Up-Regulation, pubmed-meshheading:20458283-Vascular Endothelial Growth Factor A
pubmed:year
2010
pubmed:articleTitle
Cellular and molecular mechanisms regulating the hepatic erythropoietin expression during acute-phase response: a role for IL-6.
pubmed:affiliation
Department of Gastroenterology and Endocrinology, Center of Internal Medicine, University of Göttingen, Göttingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't