Linked Life Data

10411124

Source:http://linkedlifedata.com/resource/pubmed/id/10411124

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-9-1
pubmed:abstractText
Intercellular adhesion molecule-1 (ICAM-1) has been suggested to play an important role in the perpetuation of autoimmune thyroid disease. To clarify the regulation of ICAM-1 gene in thyroid cells, we investigated ICAM-1 expression in the FRTL-5 thyroid cell model and defined several elements in the 5'-regulatory region that are important for transcriptional regulation of the rat ICAM-1 gene. Cells maintained in medium with 5% serum but without hydrocortisone, insulin, and thyrotropin (TSH) express the highest levels of ICAM-1 RNA. TSH/forskolin downregulate ICAM-1 RNA levels independent of the presence or absence of hydrocortisone or insulin. Moreover, TSH/forskolin decrease ICAM-1 RNA levels that are maximally induced by two cytokines: 100 ng/mL tumor necrosis factor-alpha (TNF-alpha) or 100 U/ml interferon-gamma (IFN-gamma). The effect of TSH/forskolin, as well as TNF-alpha and IFN-gamma, on ICAM-1 RNA levels is transcriptional. Thus, we cloned a 1.8-kb fragment of the 5'-flanking region of the rat ICAM-1 gene, upstream of the translational start site, and showed that TNF-alpha or IFN-gamma caused a 3.5- and greater than 12-fold increase respectively, in its promoter activity, when linked to a luciferase reporter gene and stably transfected into FRTL-5 cells. TSH or forskolin, in contrast, halved the activity of the full length chimera within 24 hours and significantly suppressed the TNF-alpha and IFN-gamma-induced increase (>50%; p < 0.02). Using 5'-deletion mutants, we located the element important for the TNF-alpha effect between -431 and -175 bp; we additionally show that deletion of a NF-kappaB core element within this region, TTGGAAATTC (-240 to -230 bp), causes the loss of TNF-alpha inducibility. The effect of IFN-gamma could be localized between -175 bp and -97 bp from the start of translation. This region contains 2 regulatory elements known to be involved in IFN-gamma action in other eukaryotic cells, an IFN-gamma activated site (GAS), -138 to -128 bp, and Spl site, -112 to -108 bp. Deletion of the 10 bp GAS sequence resulted in the complete loss of IFN-gamma induction of pCAM-175 promoter activity. TSH and forskolin action was also mapped between -175 bp and -97 bp from the start of translation. The mutant construct, pCAM-175delGAS mutl, which has no GAS sequence, exhibited no TSH-mediated suppression of promoter activity. We thus show that TSH/cAMP can downregulate ICAM-1 gene expression and inhibit the activity of cytokines (TNF-alpha and IFN-gamma) to increase ICAM-1 gene expression in FRTL-5 thyroid cells. We also localized elements on the 5'-flanking region of ICAM-1 important for these actions. We propose that this TSH/cyclic adenosine monophosphate (cAMP) action is a component of the mechanism to preserve self-tolerance of the thyroid during hormone-induced growth and function of the gland, and it may attenuate cytokine action during inflammatory reactions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1050-7256
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
601-12
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10411124-Animals, pubmed-meshheading:10411124-Base Sequence, pubmed-meshheading:10411124-Blotting, Northern, pubmed-meshheading:10411124-Cell Line, pubmed-meshheading:10411124-Cloning, Molecular, pubmed-meshheading:10411124-Gene Expression Regulation, pubmed-meshheading:10411124-Intercellular Adhesion Molecule-1, pubmed-meshheading:10411124-Luciferases, pubmed-meshheading:10411124-Molecular Sequence Data, pubmed-meshheading:10411124-Promoter Regions, Genetic, pubmed-meshheading:10411124-RNA, Messenger, pubmed-meshheading:10411124-Rats, pubmed-meshheading:10411124-Rats, Inbred BUF, pubmed-meshheading:10411124-Recombinant Fusion Proteins, pubmed-meshheading:10411124-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:10411124-Sequence Deletion, pubmed-meshheading:10411124-Terminal Repeat Sequences, pubmed-meshheading:10411124-Thyroid Gland, pubmed-meshheading:10411124-Thyroid Hormones, pubmed-meshheading:10411124-Transfection
pubmed:year
1999
pubmed:articleTitle
Hormone-dependent regulation of intercellular adhesion molecule-1 gene expression: cloning and analysis of 5'-regulatory region of rat intercellular adhesion molecule-1 gene in FRTL-5 rat thyroid cells.
pubmed:affiliation
Department of Internal Medicine, School of Medicine, Chungnam National University, Taejon, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't