| PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells. | |
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MedLine Citation:
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PMID: 20498301 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prostaglandin E(2) (PGE(2)) is an inflammatory mediator often used to increase CCR7 expression in the dendritic cells (DCs) used as cancer vaccines and to enhance their responsiveness to lymph node-associated chemokines. Here, we show that high surface expression of CCR7 on PGE(2)-matured DCs is associated with their suppressed production of the endogenous CCR7 ligand, CCL19, and is reversible by exogenous CCL19. In contrast to the PGE(2)-matured DCs, DCs matured in the presence of toll-like receptor (TLR) ligands and interferons produce high levels of both CCL19 and CCR7 mRNA/protein, but show selectively reduced expression of surface CCR7, which is compensated after DC removal from the CCL19-rich maturation environment. In accordance with these findings, PGE(2)-matured DCs show significantly higher in vitro migratory responsiveness to lymph node-associated chemokines directly after DC generation, but not after additional short-term culture in vitro, nor in vivo in patients injected with (111)indium-labeled DCs. The differences in CCL19-producing ability imprinted during DC maturation result in their different abilities to attract CCR7(+) naive T cells. Our data help to explain the impact of PGE(2) on CCR7 expression in maturing DCs and demonstrate a novel mechanism of regulatory activity of PGE(2), mediated by the inhibition of DCs ability to attract naive T cells. |
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Authors:
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Ravikumar Muthuswamy; Jan Mueller-Berghaus; Uwe Haberkorn; Todd A Reinhart; Dirk Schadendorf; Pawel Kalinski |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-24 |
Journal Detail:
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Title: Blood Volume: 116 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-03 Completed Date: 2010-10-07 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 1454-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery, University of Pittsburgh, PA 15213-1863, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Cell Adhesion Cell Movement Chemokine CCL19 / metabolism* Dendritic Cells / drug effects*, metabolism Dinoprostone / pharmacology* Enzyme-Linked Immunosorbent Assay Humans Leukocytes, Mononuclear / cytology, drug effects, metabolism Lymph Nodes / cytology, drug effects, metabolism Melanoma / drug therapy, immunology, metabolism Monocytes / cytology, drug effects, metabolism Receptors, CCR7 / metabolism* T-Lymphocytes / physiology* Toll-Like Receptors |
| Grant Support | |
ID/Acronym/Agency:
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CA121973/CA/NCI NIH HHS; CA132714/CA/NCI NIH HHS; CA134633/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CCR7 protein, human; 0/Chemokine CCL19; 0/Receptors, CCR7; 0/Toll-Like Receptors; 363-24-6/Dinoprostone |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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