Linked Life Data

10640755

Source:http://linkedlifedata.com/resource/pubmed/id/10640755

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-2-24
pubmed:abstractText
Activation of lamina propria (LP) T cells via the CD2 pathway enhances IFN-gamma (IFN-gamma) secretion with further enhancement after CD28 coligation. The molecular mechanisms regulating IFN-gamma expression in LP T cells remain unknown. Previous studies in PBL and T cell lines identified cis- and trans-regulatory elements in TCR-mediated expression of IFN-gamma. This study examines CD2 and PMA/ionophore-responsive IFN-gamma promoter elements. Activation of LPMC via CD2-induced IFN-gamma secretion and a parallel up-regulation of mRNA expression. CD28 coligation enhanced mRNA stability without up-regulating transcription as measured by nuclear run-on. Transfection of a -2.7-kb IFN-gamma promoter-reporter construct into PBL and LP mononuclear cells (LPMC) revealed significant promoter activity after CD2 activation, with additional transactivation after CD2/CD28 costimulation in PBL, but not in LPMC. Functional analysis using truncated promoter fragments identified distinct cis-regulatory regions selectively transactivating IFN-gamma expression in PBL compared with LPMC. In PBL, CD2 activation elements reside within the -108- to +64-bp region. However, in LPMC the upstream region between -204 and -108 bp was essential. Transfection of the proximal and distal AP-1-binding elements, as well as TRE/AP-1 constructs, revealed functional activation of AP-1 subsequent to CD2 signaling, with activation critical in PBL but diminished in LPMC. Electromobility shift analysis using oligonucleotides encompassing the proximal, distal, and BED/AP-1-binding regions failed to demonstrate selective transactivation after CD2 signaling of LPMC. This report provides evidence that activation of LPMC results in transactivation of multiple promoter elements regulating IFN-gamma expression distinct from those in PBL.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1399-407
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10640755-5' Untranslated Regions, pubmed-meshheading:10640755-Adjuvants, Immunologic, pubmed-meshheading:10640755-Antigens, CD2, pubmed-meshheading:10640755-Antigens, CD28, pubmed-meshheading:10640755-Conserved Sequence, pubmed-meshheading:10640755-Humans, pubmed-meshheading:10640755-Interferon-gamma, pubmed-meshheading:10640755-Intestinal Mucosa, pubmed-meshheading:10640755-Leukocytes, Mononuclear, pubmed-meshheading:10640755-Lymphocyte Activation, pubmed-meshheading:10640755-Promoter Regions, Genetic, pubmed-meshheading:10640755-Protein Binding, pubmed-meshheading:10640755-RNA, Messenger, pubmed-meshheading:10640755-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:10640755-Signal Transduction, pubmed-meshheading:10640755-T-Lymphocyte Subsets, pubmed-meshheading:10640755-Transcription Factor AP-1, pubmed-meshheading:10640755-Transcriptional Activation, pubmed-meshheading:10640755-Up-Regulation
pubmed:year
2000
pubmed:articleTitle
Mucosa-specific targets for regulation of IFN-gamma expression: lamina propria T cells use different cis-elements than peripheral blood T cells to regulate transactivation of IFN-gamma expression.
pubmed:affiliation
Inflammatory Bowel Disease Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't