Document Detail


Transcriptional control mechanisms associated with the nucleotide receptor P2X7, a critical regulator of immunologic, osteogenic, and neurologic functions.
MedLine Citation:
PMID:  21298493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nucleotide receptor P2X(7) is an attractive therapeutic target and potential biomarker for multiple inflammatory and neurologic disorders, and it is expressed in several immune, osteogenic, and neurologic cell types. Aside from its role in the nervous system, it is activated by ATP released at sites of tissue damage, inflammation, and infection. Ligand binding to P2X(7) stimulates many cell responses, including calcium fluxes, MAPK activation, inflammatory mediator release, and apoptosis. Much work has centered on P2X(7) action in cell death and mediator processing (e.g., pro-interleukin-1 cleavage by the inflammasome), but the contribution of P2X(7) to transcriptional regulation is less well defined. This review will focus on the growing evidence for the importance of nucleotide-mediated gene expression, highlight several animal models, human genetic, and clinical studies that support P2X(7) as a therapeutic target, and discuss the latest developments in anti-P2X(7) clinical trials.
Authors:
Lisa Y Lenertz; Monica L Gavala; Yiming Zhu; Paul J Bertics
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Immunologic research     Volume:  50     ISSN:  1559-0755     ISO Abbreviation:  Immunol. Res.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-11     Revised Date:  2012-05-25    
Medline Journal Info:
Nlm Unique ID:  8611087     Medline TA:  Immunol Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22-38     Citation Subset:  IM    
Affiliation:
Department of Biomolecular Chemistry, School of Medicine and Public Health, The University of Wisconsin-Madison, 53706, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Biological Markers / metabolism
Gene Expression Regulation*
Humans
Immunologic Factors / immunology
Inflammation / immunology
Interleukin-1beta / immunology,  metabolism
Osteogenesis / genetics*,  immunology*
Proto-Oncogene Proteins c-fos / metabolism
Receptors, Purinergic P2X7 / genetics,  immunology*
Signal Transduction / genetics,  immunology
Grant Support
ID/Acronym/Agency:
1 P01 HL0885940/HL/NHLBI NIH HHS; 1 U19 AI070503/AI/NIAID NIH HHS; 2 R01 HL069116/HL/NHLBI NIH HHS; 5 R01 CA108467/CA/NCI NIH HHS; P01 HL088594-02/HL/NHLBI NIH HHS; P01 HL088594-03/HL/NHLBI NIH HHS; P01 HL088594-04/HL/NHLBI NIH HHS; P01 HL088594-05/HL/NHLBI NIH HHS; R01 CA108467/CA/NCI NIH HHS; R01 CA108467-01/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Immunologic Factors; 0/Interleukin-1beta; 0/Proto-Oncogene Proteins c-fos; 0/Receptors, Purinergic P2X7; 56-65-5/Adenosine Triphosphate

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