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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2001-9-6
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pubmed:abstractText |
Allergic inflammatory conditions such as asthma are characterized by an accumulation of eosinophils at sites of inflammation. Eotaxin-3/CCL26 is a member of the family of CC chemokines, which are known to be potent chemoattractants for eosinophils. This chemokine was shown to be up-regulated by IL-4 and IL-13 in endothelial cells. This study demonstrates that eotaxin-3 transcription and eotaxin-3 protein expression are stimulated by IL-4 and IL-13 in a time- and dose-dependent fashion in human dermal fibroblasts. In contrast to eotaxin-1/CCL11, TNF-alpha could not act as inducer on its own nor did it synergize with IL-4. The activities of eotaxin-3 promoter luciferase constructs were significantly increased by IL-4 and IL-13 in human dermal fibroblasts. This effect was mediated by a binding site for the transcription factor STAT6 in the eotaxin-3 promoter sequence. Mutations in the STAT6 binding site abrogated up-regulation of eotaxin-3 promoter activity. In STAT6-defective human embryonic kidney 293 cells, the wild-type luciferase construct, but not the STAT6 binding mutant, was inducible by IL-4 only upon cotransfection of STAT6 expression vector. In addition, eotaxin-3 protein was detectable in the supernatants of STAT6-transfected human embryonic kidney 293 cells upon IL-4 or IL-13 stimulation. In the same experiments, TNF-alpha induced activation of the monocyte chemoattractant protein-1/CCL2 gene was independent of STAT6 transfection. These results indicate that IL-4 and IL-13 activate eotaxin-3 gene expression in a STAT6-dependent fashion. Although both eotaxin-1 and -3 are regulated by this transcription factor, the response of the eotaxin-3 gene to TNF-alpha stimulation appears to be different.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCL11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CCL26 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL11,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CC,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-13,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3216-22
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11544308-Binding Sites,
pubmed-meshheading:11544308-Cells, Cultured,
pubmed-meshheading:11544308-Chemokine CCL11,
pubmed-meshheading:11544308-Chemokine CCL2,
pubmed-meshheading:11544308-Chemokines, CC,
pubmed-meshheading:11544308-Cytokines,
pubmed-meshheading:11544308-Dose-Response Relationship, Drug,
pubmed-meshheading:11544308-Fibroblasts,
pubmed-meshheading:11544308-Gene Expression Regulation,
pubmed-meshheading:11544308-Genes, Reporter,
pubmed-meshheading:11544308-Humans,
pubmed-meshheading:11544308-Interleukin-13,
pubmed-meshheading:11544308-Interleukin-4,
pubmed-meshheading:11544308-Kidney,
pubmed-meshheading:11544308-Luciferases,
pubmed-meshheading:11544308-Organ Specificity,
pubmed-meshheading:11544308-Promoter Regions, Genetic,
pubmed-meshheading:11544308-RNA, Messenger,
pubmed-meshheading:11544308-Recombinant Fusion Proteins,
pubmed-meshheading:11544308-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11544308-STAT6 Transcription Factor,
pubmed-meshheading:11544308-Skin,
pubmed-meshheading:11544308-Th2 Cells,
pubmed-meshheading:11544308-Trans-Activators,
pubmed-meshheading:11544308-Transcription, Genetic,
pubmed-meshheading:11544308-Transfection,
pubmed-meshheading:11544308-Tumor Necrosis Factor-alpha
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pubmed:year |
2001
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pubmed:articleTitle |
Activation of eotaxin-3/CCLl26 gene expression in human dermal fibroblasts is mediated by STAT6.
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pubmed:affiliation |
Department of Allergic Diseases, Novartis Research Institute, Vienna, Austria.
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pubmed:publicationType |
Journal Article,
Comparative Study
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