Document Detail


P2Y2 receptor transcription is increased by NF-kappa B and stimulates cyclooxygenase-2 expression and PGE2 released by intestinal epithelial cells.
MedLine Citation:
PMID:  19734210     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inflammatory stresses associated with inflammatory bowel diseases up-regulate P2Y(2) mRNA receptor expression in the human colon adenocarcinoma cell line Caco-2, the noncancerous IEC-6 cells and in colonic tissues of patient suffering from Crohn's disease and ulcerative colitis. However, the transcriptional events regulating P2Y(2) receptor (P2Y(2)R) expression are not known. We have identified a putative transcription start site in the P2Y(2)R gene and demonstrated acetylation of Lys(14) on histone H3 and Lys(8) on histone H4, thus suggesting that the chromatin associated with the P2Y(2) promoter is accessible to transcription factors. We also showed that the transcription factor NF-kappaB p65 regulates P2Y(2)R transcription under both proinflammatory and basal conditions. A NF-kappaB-responsive element was identified at -181 to -172 bp in the promoter region of P2Y(2). Hence, activation of P2Y(2)R by ATP and UTP stimulated cyclooxygenase-2 expression and PGE(2) secretion by intestinal epithelial cells. These findings demonstrate that P2Y(2)R expression is regulated during intestinal inflammation through an NF-kappaB p65-dependent mechanism and could contribute not only to inflammatory bowel disease but also to other inflammatory diseases by regulating PG release.
Authors:
Emilie Degagné; Djordje M Grbic; Andrée-Anne Dupuis; Elise G Lavoie; Christine Langlois; Nishant Jain; Gary A Weisman; Jean Sévigny; Fernand-Pierre Gendron
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-04
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  183     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-21     Completed Date:  2009-11-16     Revised Date:  2011-09-22    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4521-9     Citation Subset:  AIM; IM    
Affiliation:
Canadian Institutes of Health Research Team on the Digestive Epithelium, Département d'Anatomie et de Biologie Cellulaire, Université de Sherbrooke, Sherbrooke, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Caco-2 Cells
Cell Line
Cyclooxygenase 2 / biosynthesis*,  genetics
Dinoprostone / secretion*
Humans
Inflammation Mediators / physiology
Intestinal Mucosa / cytology,  enzymology,  pathology,  secretion*
Promoter Regions, Genetic / immunology
Rats
Receptors, Purinergic P2 / biosynthesis,  genetics*,  physiology
Receptors, Purinergic P2Y2
Transcription Factor RelA / physiology*
Transcription, Genetic / immunology*
Up-Regulation / genetics*,  immunology*
Grant Support
ID/Acronym/Agency:
67520//Canadian Institutes of Health Research; 68957//Canadian Institutes of Health Research; 93683//Canadian Institutes of Health Research; AG18357/AG/NIA NIH HHS; DE07389/DE/NIDCR NIH HHS; DE17591/DE/NIDCR NIH HHS; R01 DE007389-21A1/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Inflammation Mediators; 0/P2RY2 protein, human; 0/Receptors, Purinergic P2; 0/Receptors, Purinergic P2Y2; 0/Transcription Factor RelA; 363-24-6/Dinoprostone; EC 1.14.99.1/Cyclooxygenase 2

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