Linked Life Data

19160541

Source:http://linkedlifedata.com/resource/pubmed/id/19160541

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-1-22
pubmed:abstractText
Interferon-gamma (IFN-gamma) is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-gamma has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-gamma expression. In order to achieve proper IFN-gamma-mediated immunological effects, IFN-gamma expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-gamma expression by Prospero-related Homeobox (Prox1). In Jurkat T cells and primary human CD4+ T cells, Prox1 expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-gamma expression. Reporter analysis and chromatin immunoprecipitation (ChIP) revealed that Prox1 associates with and inhibits the transcription activity of IFN-,gammapromoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Prox1 and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPPARgamma, which is also an IFN-gamma repressor in T cells. By introducing deletions and mutations into Prox1, we show that the repression of IFN-gamma promoter by Prox1 is largely dependent upon the physical interaction between Prox1 and PPPARgamma Furthermore, PPPARgammaantagonist treatment removes Prox1 from IFN-gamma promoter and attenuates repression of IFN-gamma expression by Prox1. These findings establish Prox1 as a new negative regulator of IFN-gamma expression in T cells and will aid in the understanding of IFN-gamma transcription regulation mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1001-0602
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
911-20
pubmed:meshHeading
pubmed-meshheading:19160541-Anilides, pubmed-meshheading:19160541-Animals, pubmed-meshheading:19160541-Cytokines, pubmed-meshheading:19160541-Gene Expression Regulation, pubmed-meshheading:19160541-Homeodomain Proteins, pubmed-meshheading:19160541-Humans, pubmed-meshheading:19160541-Interferon-gamma, pubmed-meshheading:19160541-Jurkat Cells, pubmed-meshheading:19160541-Lymphocyte Activation, pubmed-meshheading:19160541-Mice, pubmed-meshheading:19160541-PPAR gamma, pubmed-meshheading:19160541-Promoter Regions, Genetic, pubmed-meshheading:19160541-Protein Binding, pubmed-meshheading:19160541-Protein Interaction Mapping, pubmed-meshheading:19160541-Repressor Proteins, pubmed-meshheading:19160541-Sequence Homology, Nucleic Acid, pubmed-meshheading:19160541-T-Lymphocytes, pubmed-meshheading:19160541-Tumor Suppressor Proteins
pubmed:year
2008
pubmed:articleTitle
Repression of interferon-gamma expression in T cells by Prospero-related homeobox protein.
pubmed:affiliation
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't