Linked Life Data

17916644

Source:http://linkedlifedata.com/resource/pubmed/id/17916644

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-12-10
pubmed:abstractText
Early growth response (Egr)-1 is a transcription factor that regulates genes involved in inflammation, innate and adaptive immunity, coagulation, and wound healing; however, little is known about the role of Egr-1 in acute liver injury. We tested the hypothesis that Egr-1 is involved in acute liver injury induced by galactosamine/lipopolysaccharide (GalN/LPS). GalN/LPS exposure biphasically increased hepatic egr-1 mRNA accumulation at 1 h and again at 4-5.5 h after treatment in wild-type mice. Within 4-5.5 h after GalN/LPS exposure, wild-type mice exhibited histological evidence of hepatocyte injury, cell death, and extensive areas of hemorrhage, as well as increased plasma alanine aminotransferase activities. In contrast, these parameters were largely attenuated in egr-1(-/-) mice. The initial expression of tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1 mRNA or protein was equivalent between genotypes at 1 h after GalN/LPS administration. However, at subsequent time points, hepatic expression of these genes was decreased in egr-1(-/-) compared with wild-type mice. In addition, neutrophil extravasation from hepatic sinusoids into the liver parenchyma was decreased in egr-1(-/-) compared with wild-type mice 4 h after GalN/LPS. Whereas caspase-3 activation and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei were detected in wild-type mice at 4 and 5.5 h after GalN/LPS administration, respectively, these markers of apoptosis were delayed in egr-1(-/-) mice. Delayed development of apoptosis was associated with an extension of survival by 1 h in egr-1(-/-) compared with wild-type mice. These data demonstrate that Egr-1 plays an important role in acceleration of hepatic inflammation, apoptosis, and subsequent mortality in GalN/LPS-induced acute liver injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G1124-33
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Early growth response-1 contributes to galactosamine/lipopolysaccharide-induced acute liver injury in mice.
pubmed:affiliation
Dept. of Pathobiology, Cleveland Clinic, 9500 Euclid Ave. NE40, Cleveland, OH 44195, USA. pritchm@ccf.org
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural