| Chemotherapeutic agents targeting the tubulin cytoskeleton modify LPS-induced cytokine secretion by dendritic cells and increase antigen presentation. | |
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MedLine Citation:
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PMID: 20386470 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent studies support the idea that certain chemotherapeutic agents do not act only by cytotoxicity, but also have immunomodulatory activity. Because of their role in mitosis chemotherapeutic agents targeting microtubules are widely used, and this study determined the outcome of disturbing tubulin cytoskeleton dynamics on human dendritic cell function. Dendritic cells (DCs) play a major role in the generation of the adaptive immune response owing to their capacity for antigen presentation leading to T lymphocyte activation and differentiation and there is compelling evidence for their contribution to the antitumoral immune response. Two agents that target the tubulin cytoskeleton were used, taxol and colchicine, and a brief pretreatment with either increased antigen presentation by DCs independently of significant phenotypic change, cell death, or cytokine production. Although taxol and colchicine use different mechanisms to disrupt microtubules, NF-kappabeta was activated by either. We therefore determined whether the cytokine secretion profile in response to lipopolysaccharide (LPS) was modified. LPS stimulation of DCs induced IL-10, IL-12p70, TNFalpha and IL-1beta secretion, and taxol pretreatment modified this response by down-regulating IL-1beta secretion whereas colchicine induced a proinflammatory cytokine profile with reduced IL-10 and increased IL-12p70 and TNFalpha secretion. Taken together, these data reveal new immunomodulatory strategies of microtubule disrupting agents in dendritic cells, that of modifying the cytokine response to LPS and that of increasing T lymphocyte activation without induction of inflammatory cytokine secretion by dendritic cells. |
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Authors:
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Viviana Marin-Esteban; Dominique Charron; Catherine Gelin; Nuala Mooney |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunotherapy (Hagerstown, Md. : 1997) Volume: 33 ISSN: 1537-4513 ISO Abbreviation: J. Immunother. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-28 Completed Date: 2010-09-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9706083 Medline TA: J Immunother Country: United States |
Other Details:
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Languages: eng Pagination: 364-70 Citation Subset: IM |
Affiliation:
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Institut Universitaire d'Hématologie, Université Paris-Diderot-Paris 7, INSERM Unité 940, Hématologie, Immunologie, Cibles thérapeutiques, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigen Presentation
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drug effects Antineoplastic Agents / pharmacology* Cells, Cultured Colchicine / pharmacology* Cytokines / secretion Cytoskeleton / drug effects* Dendritic Cells / drug effects*, immunology*, metabolism, pathology Drug Interactions Humans Lipopolysaccharides / metabolism, pharmacology Lymphocyte Activation / drug effects NF-kappa B / metabolism Neoplasms / drug therapy*, immunology Paclitaxel / pharmacology* T-Lymphocytes / immunology Tubulin / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Cytokines; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Tubulin; 33069-62-4/Paclitaxel; 64-86-8/Colchicine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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