Linked Life Data

9421426

Source:http://linkedlifedata.com/resource/pubmed/id/9421426

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-15
pubmed:abstractText
Aberrant expression of major histocompatibility complex (MHC) class II proteins on thyrocytes, which is associated with autoimmune thyroid disease, is mimicked by gamma-interferon (gamma-IFN). To define elements and factors that regulate class II gene expression in thyrocytes and that might be involved in aberrant expression, we have studied gamma-IFN-induced HLA-DR alpha gene expression in rat FRTL-5 thyroid cells. The present report shows that class II expression in FRTL-5 thyrocytes is positively regulated by the class II transactivator (CIITA), and that CIITA mimics the action of gamma-IFN. Thus, as is the case for gamma-IFN, several distinct and highly conserved elements on the 5'-flanking region of the HLA-DR alpha gene, the S, X1, X2, and Y boxes between -137 to -65 bp, are required for class II gene expression induced by pCIITA transfection in FRTL-5 thyroid cells. CIITA and gamma-IFN do not cause additive increases in HLA-DR alpha gene expression in FRTL-5 cells, consistent with the possibility that CIITA is an intermediate factor in the gamma-IFN pathway to increased class II gene expression. Additionally, gamma-IFN treatment of FRTL-5 cells induces an endogenous CIITA transcript; pCIITA transfection mimics the ability of gamma-IFN treatment of FRTL-5 thyroid cells to increase the formation of a specific and novel protein/DNA complex containing CBP, a coactivator of CRE binding proteins important for cAMP-induced gene expression; and the action of both gamma-IFN and CIITA to increase class II gene expression and increase complex formation is reduced by cotransfection of a thyroid Y box protein, which suppresses MHC class I gene expression in FRTL-5 thyroid cells and is a homolog of human YB-1, which suppresses MHC class II expression in human glioma cells. We conclude that CIITA and TSH receptor suppressor element binding protein-1 are components of the gamma-IFN-regulated transduction system which, respectively, increase or decrease class II gene expression in thyrocytes and may, therefore, be involved in aberrant class II expression associated with autoimmune thyroid disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/HLA-DR Antigens, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma, http://linkedlifedata.com/resource/pubmed/chemical/MHC class II transactivator protein, http://linkedlifedata.com/resource/pubmed/chemical/NFI Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Y-Box-Binding Protein 1, http://linkedlifedata.com/resource/pubmed/chemical/YBX1 protein, human
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
280-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Major histocompatibility class II HLA-DR alpha gene expression in thyrocytes: counter regulation by the class II transactivator and the thyroid Y box protein.
pubmed:affiliation
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't