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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-1-6
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pubmed:databankReference |
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pubmed:abstractText |
We have previously shown that colonic epithelial cells are a major site of MIP-3alpha production in human colon and that enterocyte MIP-3alpha protein levels are elevated in inflammatory bowel disease. The aim of this study was to determine the molecular mechanisms regulating MIP-3alpha gene transcription in Caco-2 intestinal epithelial cells. We show that a kappaB element at nucleotides -82 to -93 of the MIP-3alpha promoter binds p50/p65 NF-kappaB heterodimers and is a major regulator of basal and interleukin-1beta (IL-1beta)-mediated gene activation. Scanning mutagenesis of the MIP-3alpha 5'-flanking region also identified two additional binding elements: Site X (nucleotides -63 to -69) and Site Y (nucleotides -143 to -154). Site X (CGCCTTC) bound Sp1 and regulated basal MIP-3alpha gene transcription. Overexpression of Sp1 increased basal luciferase activity, whereas, substitutions in the Sp1 element significantly reduced reporter activity. In contrast, Site Y (AAGCAGGAAGTT) regulated both basal and cytokine-induced gene activation and bound the Ets nuclear factor ESE-1. Substitutions in the Site Y element markedly reduced inducible MIP-3alpha reporter activity. Conversely, overexpression of ESE-1 significantly up-regulated MIP-3alpha luciferase levels. Taken together, our findings demonstrate that co-ordinate activation and binding of ESE-1, Sp1, and NF-kappaB to the MIP-3alpha promoter is required for maximal gene expression by cytokine-stimulated Caco-2 human intestinal epithelial cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CCL20 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CCR6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL20,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CC,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ELF3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR6,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sp3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
875-84
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12414801-Base Sequence,
pubmed-meshheading:12414801-Binding Sites,
pubmed-meshheading:12414801-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:12414801-Caco-2 Cells,
pubmed-meshheading:12414801-Chemokine CCL20,
pubmed-meshheading:12414801-Chemokines, CC,
pubmed-meshheading:12414801-Cloning, Molecular,
pubmed-meshheading:12414801-DNA-Binding Proteins,
pubmed-meshheading:12414801-Gene Expression Regulation,
pubmed-meshheading:12414801-Humans,
pubmed-meshheading:12414801-Interleukin-1,
pubmed-meshheading:12414801-Macrophage Inflammatory Proteins,
pubmed-meshheading:12414801-Molecular Sequence Data,
pubmed-meshheading:12414801-NF-kappa B,
pubmed-meshheading:12414801-Promoter Regions, Genetic,
pubmed-meshheading:12414801-Proto-Oncogene Proteins,
pubmed-meshheading:12414801-Receptors, CCR6,
pubmed-meshheading:12414801-Receptors, Chemokine,
pubmed-meshheading:12414801-Sp1 Transcription Factor,
pubmed-meshheading:12414801-Sp3 Transcription Factor,
pubmed-meshheading:12414801-Trans-Activators,
pubmed-meshheading:12414801-Transcription, Genetic,
pubmed-meshheading:12414801-Transcription Factors,
pubmed-meshheading:12414801-Transcriptional Activation
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pubmed:year |
2003
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pubmed:articleTitle |
ESE-1, an enterocyte-specific Ets transcription factor, regulates MIP-3alpha gene expression in Caco-2 human colonic epithelial cells.
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pubmed:affiliation |
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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