|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021747,
umls-concept:C0033684,
umls-concept:C0185117,
umls-concept:C0376298,
umls-concept:C0439677,
umls-concept:C0851285,
umls-concept:C0919490,
umls-concept:C1321919,
umls-concept:C1336636,
umls-concept:C2911684
|
|
pubmed:issue |
13
|
|
pubmed:dateCreated |
2000-5-4
|
|
pubmed:abstractText |
The protein product of the Toll-like receptor (TLR) 4 gene has been implicated in the signal transduction events induced by lipopolysaccharide (LPS). In mice, destructive mutations of Tlr4 impede the normal response to LPS and cause a high susceptibility to Gram-negative infection. Expression of TLR4 mRNA in humans is restricted to a small number of cell types, including LPS-responsive myeloid cells, B-cells, and endothelial cells. To investigate the molecular basis for TLR4 expression in cells of myeloid origin, we cloned the human TLR4 gene and analyzed its putative 5'-proximal promoter. In transient transfections a region of only 75 base pairs upstream of the major transcription initiation site was sufficient to induce maximal luciferase activity in THP-1 cells. The sequence of this region is similar in human and mouse TLR4 genes and lacks a TATA box, typical Sp1-sites or CCAAT box sequences. Instead, it contains consensus-binding sites for Ets family transcription factors, octamer-binding factors, and a composite interferon response factor/Ets motif. The activity of the promoter in macrophages was strictly dependent on the integrity of both half sites of the composite interferon response factor/Ets motif, which was constitutively bound by the myeloid and B-cell-specific transcription factor PU.1 and interferon consensus sequence-binding protein. These results indicate that the two tissue-restricted transcription factors PU.1 and interferon consensus sequence-binding protein participate in the basal regulation of human TLR4 in myeloid cells. Cloning of the human TLR4 gene provides a basis for further investigation of the possible impact of genetic variations on the susceptibility to infection and sepsis.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-8,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
31
|
|
pubmed:volume |
275
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
9773-81
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:10734131-Amino Acid Sequence,
pubmed-meshheading:10734131-Animals,
pubmed-meshheading:10734131-Base Sequence,
pubmed-meshheading:10734131-Bone Marrow,
pubmed-meshheading:10734131-Cloning, Molecular,
pubmed-meshheading:10734131-DNA,
pubmed-meshheading:10734131-Drosophila Proteins,
pubmed-meshheading:10734131-Gene Expression Regulation,
pubmed-meshheading:10734131-Humans,
pubmed-meshheading:10734131-Interferon Regulatory Factors,
pubmed-meshheading:10734131-Membrane Glycoproteins,
pubmed-meshheading:10734131-Mice,
pubmed-meshheading:10734131-Molecular Sequence Data,
pubmed-meshheading:10734131-Mutagenesis, Site-Directed,
pubmed-meshheading:10734131-Promoter Regions, Genetic,
pubmed-meshheading:10734131-Protein Binding,
pubmed-meshheading:10734131-Proto-Oncogene Proteins,
pubmed-meshheading:10734131-Receptors, Cell Surface,
pubmed-meshheading:10734131-Repressor Proteins,
pubmed-meshheading:10734131-Sequence Homology, Nucleic Acid,
pubmed-meshheading:10734131-Toll-Like Receptor 4,
pubmed-meshheading:10734131-Toll-Like Receptors,
pubmed-meshheading:10734131-Trans-Activators
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human Toll-like receptor 4 gene.
|
|
pubmed:affiliation |
Department of Hematology and Oncology, University of Regensburg, 93042 Regensburg, Germany. Michael.Rehli@klinik.uni-regensburg.de
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
