Source:http://linkedlifedata.com/resource/pubmed/id/19915048
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2009-11-20
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pubmed:abstractText |
Protective humoral immune responses critically depend on the optimal differentiation of B cells into Ab-secreting cells. Because of the important role of Abs in fighting infections and in successful vaccination, it is imperative to identify mediators that control B cell differentiation. Activation of B cells through TLR9 by CpG-DNA induces plasma cell differentiation and Ab production. Herein, we examined the role of the peroxisome proliferator-activated receptor (PPAR)gamma/RXRalpha pathway on human B cell differentiation. We demonstrated that activated B cells up-regulate their expression of PPARgamma. We also show that nanomolar levels of natural (15-deoxy-Delta(12,14)-prostaglandin J(2)) or synthetic (rosiglitazone) PPARgamma ligands enhanced B cell proliferation and significantly stimulated plasma cell differentiation and Ab production. Moreover, the addition of GW9662, a specific PPARgamma antagonist, abolished these effects. Retinoid X receptor (RXR) is the binding partner for PPARgamma and is required to produce an active transcriptional complex. The simultaneous addition of nanomolar concentrations of the RXRalpha ligand (9-cis-retinoic acid) and PPARgamma ligands to CpG-activated B cells resulted in additive effects on B cell proliferation, plasma cell differentiation, and Ab production. Furthermore, PPARgamma ligands alone or combined with 9-cis-retinoic acid enhanced CpG-induced expression of Cox-2 and the plasma cell transcription factor BLIMP-1. Induction of these important regulators of B cell differentiation provides a possible mechanism for the B cell-enhancing effects of PPARgamma ligands. These new findings indicate that low doses of PPARgamma/RXRalpha ligands could be used as a new type of adjuvant to stimulate Ab production.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/DE007202,
http://linkedlifedata.com/resource/pubmed/grant/DE011390,
http://linkedlifedata.com/resource/pubmed/grant/ES01247,
http://linkedlifedata.com/resource/pubmed/grant/P30 ES001247-35,
http://linkedlifedata.com/resource/pubmed/grant/R01 DE011390-22,
http://linkedlifedata.com/resource/pubmed/grant/T32 DE007202-19,
http://linkedlifedata.com/resource/pubmed/grant/T32 HL007152-33,
http://linkedlifedata.com/resource/pubmed/grant/T32HL007152
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/PRDM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoid X Receptor alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6903-12
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:19915048-Antibody Formation,
pubmed-meshheading:19915048-B-Lymphocytes,
pubmed-meshheading:19915048-Blotting, Western,
pubmed-meshheading:19915048-Cell Differentiation,
pubmed-meshheading:19915048-Cell Proliferation,
pubmed-meshheading:19915048-Cyclooxygenase 2,
pubmed-meshheading:19915048-Flow Cytometry,
pubmed-meshheading:19915048-Gene Expression,
pubmed-meshheading:19915048-Gene Expression Regulation,
pubmed-meshheading:19915048-Humans,
pubmed-meshheading:19915048-Ligands,
pubmed-meshheading:19915048-Lymphocyte Activation,
pubmed-meshheading:19915048-PPAR gamma,
pubmed-meshheading:19915048-Repressor Proteins,
pubmed-meshheading:19915048-Retinoid X Receptor alpha,
pubmed-meshheading:19915048-Transfection,
pubmed-meshheading:19915048-Up-Regulation
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pubmed:year |
2009
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pubmed:articleTitle |
Peroxisome proliferator-activated receptor gamma ligands enhance human B cell antibody production and differentiation.
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pubmed:affiliation |
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, 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,
Research Support, N.I.H., Extramural
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