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Article: Aspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells

TitleAspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells
Authors
Issue Date2001
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal of Immunology, 2001, v. 166 n. 12, p. 7053-7062 How to Cite?
AbstractAspirin is the most commonly used analgesic and antiinflammatory agent. In this study, at physiological concentrations, it profoundly inhibited CD40, CD80, CD86, and MHC class II expression on murine, GM-CSF + IL-4 stimulated, bone marrow-derived myeloid dendritic cells (DC). CD11c and MHC class I expression were unaffected. The inhibitory action was dose dependent and was evident at concentrations higher than those necessary to inhibit PG synthesis. Experiments with indomethacin revealed that the effects of aspirin on DC maturation were cyclooxygenase independent. Nuclear extracts of purified, aspirin-treated DC revealed a decreased NF-kappaB DNA-binding activity, whereas Ab supershift analysis indicated that aspirin targeted primarily NF-kappaB p50. Unexpectedly, aspirin promoted the generation of CD11c+ DC, due to apparent suppression of granulocyte development. The morphological and ultrastructural appearance of aspirin-treated cells was consistent with immaturity. Aspirin-treated DC were highly efficient at Ag capture, via both mannose receptor-mediated endocytosis and macropinocytosis. By contrast, they were poor stimulators of naive allogeneic T cell proliferation and induced lower levels of IL-2 in responding T cells. They also exhibited impaired IL-12 expression and did not produce IL-10 after LPS stimulation. Assessment of the in vivo function of aspirin-treated DC, pulsed with the hapten trinitrobenzenesulfonic acid, revealed an inability to induce normal cell-mediated contact hypersensitivity, despite the ability of the cells to migrate to T cell areas of draining lymphoid tissue. These data provide new insight into the immunopharmacology of aspirin and suggest a novel approach to the manipulation of DC for therapeutic application.
Persistent Identifierhttp://hdl.handle.net/10722/49343
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHackstein, Hen_HK
dc.contributor.authorMorelli, AEen_HK
dc.contributor.authorLarregina, ATen_HK
dc.contributor.authorGanster, RWen_HK
dc.contributor.authorPapworth, GDen_HK
dc.contributor.authorLogar, AJen_HK
dc.contributor.authorWatkins, SCen_HK
dc.contributor.authorFalo, LDen_HK
dc.contributor.authorThomson, AWen_HK
dc.date.accessioned2008-06-12T06:39:55Z-
dc.date.available2008-06-12T06:39:55Z-
dc.date.issued2001en_HK
dc.identifier.citationJournal of Immunology, 2001, v. 166 n. 12, p. 7053-7062en_HK
dc.identifier.issn0022-1767en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49343-
dc.description.abstractAspirin is the most commonly used analgesic and antiinflammatory agent. In this study, at physiological concentrations, it profoundly inhibited CD40, CD80, CD86, and MHC class II expression on murine, GM-CSF + IL-4 stimulated, bone marrow-derived myeloid dendritic cells (DC). CD11c and MHC class I expression were unaffected. The inhibitory action was dose dependent and was evident at concentrations higher than those necessary to inhibit PG synthesis. Experiments with indomethacin revealed that the effects of aspirin on DC maturation were cyclooxygenase independent. Nuclear extracts of purified, aspirin-treated DC revealed a decreased NF-kappaB DNA-binding activity, whereas Ab supershift analysis indicated that aspirin targeted primarily NF-kappaB p50. Unexpectedly, aspirin promoted the generation of CD11c+ DC, due to apparent suppression of granulocyte development. The morphological and ultrastructural appearance of aspirin-treated cells was consistent with immaturity. Aspirin-treated DC were highly efficient at Ag capture, via both mannose receptor-mediated endocytosis and macropinocytosis. By contrast, they were poor stimulators of naive allogeneic T cell proliferation and induced lower levels of IL-2 in responding T cells. They also exhibited impaired IL-12 expression and did not produce IL-10 after LPS stimulation. Assessment of the in vivo function of aspirin-treated DC, pulsed with the hapten trinitrobenzenesulfonic acid, revealed an inability to induce normal cell-mediated contact hypersensitivity, despite the ability of the cells to migrate to T cell areas of draining lymphoid tissue. These data provide new insight into the immunopharmacology of aspirin and suggest a novel approach to the manipulation of DC for therapeutic application.en_HK
dc.format.extent420 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThis is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (The AAI), publisher of The JI, holds the copyright to this manuscript. This manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). The AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.orgen_HK
dc.subject.meshAspirin - pharmacologyen_HK
dc.subject.meshDendritic Cells - drug effects - enzymology - immunology - transplantationen_HK
dc.subject.meshGrowth Inhibitors - pharmacologyen_HK
dc.subject.meshImmunosuppressive Agents - pharmacologyen_HK
dc.subject.meshLymphocyte Activation - drug effectsen_HK
dc.titleAspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-1767&volume=166&issue=12&spage=7053&epage=7062&date=2001&atitle=Aspirin+inhibits+in+vitro+maturation+and+in+vivo+immunostimulatory+function+of+murine+myeloid+dendritic+cellsen_HK
dc.identifier.emailGanster, RW: ganster@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid11390449-
dc.identifier.scopuseid_2-s2.0-0035877053-
dc.identifier.hkuros89273-
dc.identifier.isiWOS:000170949000007-

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