Linked Life Data

15383601

Source:http://linkedlifedata.com/resource/pubmed/id/15383601

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-9-22
pubmed:abstractText
The role of IL-1beta in inflammation is amply documented, but its ability to inhibit myofibroblast differentiation and, in particular, the suppression of alpha-smooth muscle actin (alpha-SMA) gene expression is less well understood. Because IL-1beta can induce C/EBPbeta expression, the role of C/EBPbeta isoforms in IL-1beta regulation of alpha-SMA gene expression was investigated in rat lung myofibroblasts. The results showed that IL-1beta inhibited alpha-SMA expression in a dose-dependent manner, which was associated with stimulation of the expression of both C/EBPbeta isoforms, liver-enriched activating protein (LAP) and liver-enriched inhibitory protein (LIP). However, a greater increase in LIP relative to LAP expression resulted in a reduced LAP/LIP ratio after IL-1beta treatment. Transfection with an LAP-expressing plasmid stimulated, whereas an LIP-expressing plasmid inhibited, alpha-SMA expression. Cells from C/EBPbeta-deficient mice had reduced levels of alpha-SMA expression and promoter activity, which failed to respond to IL-1beta treatment. Sequence analysis identified the presence of a C/EBPbeta consensus binding sequence in the alpha-SMA promoter, which, when mutated, resulted in diminished promoter activity and abolished its responsiveness to IL-1beta treatment. EMSA revealed binding of C/EBPbeta to this C/EBPbeta consensus binding sequence from the alpha-SMA promoter. Finally, IL-1beta enhanced the expression of eukaryotic initiation factor 4E, a stimulator of LIP expression, which may account for a mechanism by which IL-1beta could alter the LAP/LIP ratio. These data taken together suggest that C/EBPbeta isoforms regulate alpha-SMA gene expression, and that its inhibition by IL-1beta was due to preferential stimulation of LIP expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
173
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4661-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15383601-Actins, pubmed-meshheading:15383601-Animals, pubmed-meshheading:15383601-Blotting, Western, pubmed-meshheading:15383601-CCAAT-Enhancer-Binding Protein-beta, pubmed-meshheading:15383601-Cells, Cultured, pubmed-meshheading:15383601-Consensus Sequence, pubmed-meshheading:15383601-Eukaryotic Initiation Factor-4E, pubmed-meshheading:15383601-Female, pubmed-meshheading:15383601-Fibroblasts, pubmed-meshheading:15383601-Gene Expression Regulation, pubmed-meshheading:15383601-Interleukin-1, pubmed-meshheading:15383601-Male, pubmed-meshheading:15383601-Mice, pubmed-meshheading:15383601-Mice, Inbred C57BL, pubmed-meshheading:15383601-Mice, Knockout, pubmed-meshheading:15383601-Muscle, Smooth, pubmed-meshheading:15383601-Promoter Regions, Genetic, pubmed-meshheading:15383601-Protein Binding, pubmed-meshheading:15383601-Protein Isoforms, pubmed-meshheading:15383601-Rats, pubmed-meshheading:15383601-Rats, Inbred F344, pubmed-meshheading:15383601-Transfection
pubmed:year
2004
pubmed:articleTitle
CCAAT/enhancer-binding protein beta isoforms and the regulation of alpha-smooth muscle actin gene expression by IL-1 beta.
pubmed:affiliation
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.