DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Eun Shin | ko |
dc.contributor.author | You, Soon Hee | ko |
dc.contributor.author | Kim, Ho | ko |
dc.contributor.author | Kwon, O Yu | ko |
dc.contributor.author | Ro, Heung Kyu | ko |
dc.contributor.author | Cho, Bo Youn | ko |
dc.contributor.author | Taniguchi, Shin Ichi | ko |
dc.contributor.author | Kohn, Leonard D | ko |
dc.contributor.author | Shong, Minho | ko |
dc.date.accessioned | 2023-04-14T01:01:35Z | - |
dc.date.available | 2023-04-14T01:01:35Z | - |
dc.date.created | 2023-04-12 | - |
dc.date.created | 2023-04-12 | - |
dc.date.issued | 1999-06 | - |
dc.identifier.citation | THYROID, v.9, no.6, pp.601 - 612 | - |
dc.identifier.issn | 1050-7256 | - |
dc.identifier.uri | http://hdl.handle.net/10203/306246 | - |
dc.description.abstract | 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-I 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-I 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-KB 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 mut1, 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-I 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. | - |
dc.language | English | - |
dc.publisher | MARY ANN LIEBERT INC PUBL | - |
dc.title | 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 | - |
dc.type | Article | - |
dc.identifier.wosid | 000081124300013 | - |
dc.identifier.scopusid | 2-s2.0-0033049025 | - |
dc.type.rims | ART | - |
dc.citation.volume | 9 | - |
dc.citation.issue | 6 | - |
dc.citation.beginningpage | 601 | - |
dc.citation.endingpage | 612 | - |
dc.citation.publicationname | THYROID | - |
dc.identifier.doi | 10.1089/thy.1999.9.601 | - |
dc.contributor.localauthor | Shong, Minho | - |
dc.contributor.nonIdAuthor | Park, Eun Shin | - |
dc.contributor.nonIdAuthor | You, Soon Hee | - |
dc.contributor.nonIdAuthor | Kim, Ho | - |
dc.contributor.nonIdAuthor | Kwon, O Yu | - |
dc.contributor.nonIdAuthor | Ro, Heung Kyu | - |
dc.contributor.nonIdAuthor | Cho, Bo Youn | - |
dc.contributor.nonIdAuthor | Taniguchi, Shin Ichi | - |
dc.contributor.nonIdAuthor | Kohn, Leonard D | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | TUMOR-NECROSIS-FACTOR | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | THYROTROPIN RECEPTOR | - |
dc.subject.keywordPlus | GRAVES-DISEASE | - |
dc.subject.keywordPlus | TNF-ALPHA | - |
dc.subject.keywordPlus | SERINE PHOSPHORYLATION | - |
dc.subject.keywordPlus | FUNCTIONAL-ANALYSIS | - |
dc.subject.keywordPlus | EPITHELIAL-CELLS | - |
dc.subject.keywordPlus | INTERFERON-GAMMA | - |
dc.subject.keywordPlus | PHOSPHOLIPASE-C | - |
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