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rdf:type |
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lifeskim:mentions |
umls-concept:C0014597,
umls-concept:C0017262,
umls-concept:C0021853,
umls-concept:C0079633,
umls-concept:C0109317,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1156200,
umls-concept:C1257901,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
6
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pubmed:dateCreated |
2010-6-2
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pubmed:abstractText |
Proteinase-activated receptors (PARs) are involved in both inflammation and tumorigenesis in epithelial cells. Interleukin (IL)-8 is a potent chemoattractant and is also involved in angiogenesis. The molecular mechanism whereby PARs induce epithelial IL-8 expression is not known. In HT-29 colonic epithelial cells, PAR(1) or PAR(2) agonists stimulated the expression of IL-8 through a NF-kappaB-dependent pathway without inducing IkappaB degradation and disassociation of IkappaB from NF-kappaB. Further studies revealed that PAR activation induced the phosphorylation of p65 at Ser-276 in the nucleus, which increased the recruitment of histone acetyltransferase (HAT) p300 to p50. Inhibition of ERK activation completely blocked PAR-induced IL-8 expression, phosphorylation of p65 and HAT activity. We also demonstrated that RSK p90 was the downstream kinase that mediated ERK-induced nuclear p65 phosphorylation. In conclusion, activation of either PAR(1) or PAR(2) stimulated the transcriptional up-regulation of IL-8 in HT-29 colonic epithelial cells through a pathway that involved ERK/RSK p90, NF-kappaB phosphorylation, and HAT activity. These studies provide evidence of a new role for serine proteinases and PARs in the regulation of gene expression in colonic inflammation and tumorigenesis.
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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/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RPS6KA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, PAR-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, PAR-2,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 90-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/p300-CBP Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ribosomal protein S6 kinase...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1530-6860
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1971-80
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pubmed:meshHeading |
pubmed-meshheading:20065107-Acetylation,
pubmed-meshheading:20065107-Blotting, Western,
pubmed-meshheading:20065107-Cells, Cultured,
pubmed-meshheading:20065107-Colon,
pubmed-meshheading:20065107-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20065107-Epithelial Cells,
pubmed-meshheading:20065107-Gene Expression Regulation,
pubmed-meshheading:20065107-Histone Acetyltransferases,
pubmed-meshheading:20065107-Histones,
pubmed-meshheading:20065107-Humans,
pubmed-meshheading:20065107-I-kappa B Proteins,
pubmed-meshheading:20065107-Immunoprecipitation,
pubmed-meshheading:20065107-Interleukin-8,
pubmed-meshheading:20065107-Luciferases,
pubmed-meshheading:20065107-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:20065107-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:20065107-NF-kappa B,
pubmed-meshheading:20065107-Phosphorylation,
pubmed-meshheading:20065107-Protein Processing, Post-Translational,
pubmed-meshheading:20065107-RNA, Messenger,
pubmed-meshheading:20065107-Receptor, PAR-1,
pubmed-meshheading:20065107-Receptor, PAR-2,
pubmed-meshheading:20065107-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20065107-Ribosomal Protein S6 Kinases, 90-kDa,
pubmed-meshheading:20065107-Transfection,
pubmed-meshheading:20065107-p300-CBP Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
Proteinase-activated receptors induce interleukin-8 expression by intestinal epithelial cells through ERK/RSK90 activation and histone acetylation.
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pubmed:affiliation |
Inflammation Research Network, University of Calgary, Calgary, AB, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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