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Article: Leptin induces CD40 expression through the activation of Akt in murine dendritic cells

TitleLeptin induces CD40 expression through the activation of Akt in murine dendritic cells
Authors
Issue Date2007
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2007, v. 282 n. 38, p. 27587-27597 How to Cite?
AbstractIncreasing evidence suggests a regulatory role for leptin, an adipocyte-derived hormone, in immunity. Although recent studies indicated an essential role of leptin signaling in dendritic cell (DC) maturation, the molecular mechanisms by which leptin modulates DC functional maturation remained unclear. In this study, we showed that leptin induced CD40 expression in murine DC and significantly up-regulated their immunostimulatory function in driving T cell proliferation. Moreover, leptin markedly enhanced lipopolysaccharide- mediated DC activation. Using pharmacological inhibitors for Akt, STAT-1α, or NF-κB and the dominant negative forms of Akt and IκB kinase α/β/γ, as well as small interfering RNA for STAT-1α, we showed that Akt, STAT-1α, and NF-κB were important for the leptin- or lipopolysaccharide-induced CD40 expression. Coimmunoprecipitation analysis revealed that leptin promoted immune complex formation between Akt and the IκB kinase subunits as well as STAT-1α. Blocking the activity of Akt demonstrated a crucial role for Akt in translocation of STAT-1α and NF-κB to the nucleus and activation of the CD40 promoter. Further analysis with chromatin immunoprecipitation assay confirmed that leptin recruited STAT-1α, NF-κBp65, and RNA polymerase II to the CD40 promoter and enhanced histone 4 acetylation in a time-dependent manner. Thus, our results have elucidated the molecular mechanisms underlying leptin-induced CD40 expression and DC maturation. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/68077
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLam, QLKen_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorCao, Xen_HK
dc.contributor.authorLu, Len_HK
dc.date.accessioned2010-09-06T06:01:07Z-
dc.date.available2010-09-06T06:01:07Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2007, v. 282 n. 38, p. 27587-27597en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68077-
dc.description.abstractIncreasing evidence suggests a regulatory role for leptin, an adipocyte-derived hormone, in immunity. Although recent studies indicated an essential role of leptin signaling in dendritic cell (DC) maturation, the molecular mechanisms by which leptin modulates DC functional maturation remained unclear. In this study, we showed that leptin induced CD40 expression in murine DC and significantly up-regulated their immunostimulatory function in driving T cell proliferation. Moreover, leptin markedly enhanced lipopolysaccharide- mediated DC activation. Using pharmacological inhibitors for Akt, STAT-1α, or NF-κB and the dominant negative forms of Akt and IκB kinase α/β/γ, as well as small interfering RNA for STAT-1α, we showed that Akt, STAT-1α, and NF-κB were important for the leptin- or lipopolysaccharide-induced CD40 expression. Coimmunoprecipitation analysis revealed that leptin promoted immune complex formation between Akt and the IκB kinase subunits as well as STAT-1α. Blocking the activity of Akt demonstrated a crucial role for Akt in translocation of STAT-1α and NF-κB to the nucleus and activation of the CD40 promoter. Further analysis with chromatin immunoprecipitation assay confirmed that leptin recruited STAT-1α, NF-κBp65, and RNA polymerase II to the CD40 promoter and enhanced histone 4 acetylation in a time-dependent manner. Thus, our results have elucidated the molecular mechanisms underlying leptin-induced CD40 expression and DC maturation. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntigens, CD40 - biosynthesis - chemistry - physiologyen_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshCell Separationen_HK
dc.subject.meshDendritic Cells - cytologyen_HK
dc.subject.meshInterferon-Stimulated Gene Factor 3 - metabolismen_HK
dc.subject.meshLeptin - chemistry - metabolism - physiologyen_HK
dc.subject.meshLipopolysaccharides - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred BALB Cen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshNF-kappa B - metabolismen_HK
dc.subject.meshProto-Oncogene Proteins c-akt - metabolismen_HK
dc.subject.meshReceptors, Leptinen_HK
dc.subject.meshT-Lymphocytes - metabolismen_HK
dc.titleLeptin induces CD40 expression through the activation of Akt in murine dendritic cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=38&spage=27587&epage=27597&date=2007&atitle=Leptin+induces+CD40+expression+through+the+activation+of+AKT+in+murine+dendritic+cellsen_HK
dc.identifier.emailLam, QLK: qlam@pathology.hku.hken_HK
dc.identifier.emailZheng, BJ: bzheng@hkucc.hku.hken_HK
dc.identifier.emailJin, DY: dyjin@hku.hken_HK
dc.identifier.emailLu, L: liweilu@hkucc.hku.hken_HK
dc.identifier.authorityLam, QLK=rp00312en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityLu, L=rp00477en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M704579200en_HK
dc.identifier.pmid17660512-
dc.identifier.scopuseid_2-s2.0-34948818333en_HK
dc.identifier.hkuros132962en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34948818333&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume282en_HK
dc.identifier.issue38en_HK
dc.identifier.spage27587en_HK
dc.identifier.epage27597en_HK
dc.identifier.isiWOS:000249455600006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f1000718529419-
dc.identifier.scopusauthoridLam, QLK=8722491000en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridCao, X=7403370836en_HK
dc.identifier.scopusauthoridLu, L=7403963552en_HK
dc.identifier.citeulike3469361-

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