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2007-08-31Zeitschriftenartikel DOI: 10.1186/1471-2172-8-18
Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors
dc.contributor.authorNitsche, Andreas
dc.contributor.authorZhang, Meixia
dc.contributor.authorClauss, Theresa
dc.contributor.authorSiegert, Wolfgang
dc.contributor.authorBrune, Kay
dc.contributor.authorPahl, Andreas
dc.date.accessioned2018-05-07T13:47:11Z
dc.date.available2018-05-07T13:47:11Z
dc.date.created2010-03-23
dc.date.issued2007-08-31none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/re2tnbXniEJM/PDF/262rZEo7oSw8Y.pdf
dc.identifier.urihttp://edoc.rki.de/176904/610
dc.description.abstractBackground: Stem cell transplantation as therapy for hematological disorders is often hampered by severe graft-versus-host-disease. This may be reduced by umbilical cord blood transplantation, an effect that has been attributed to qualitative differences between neonatal and adult T cells. We compared levels of secreted proteins and cytokine mRNA induced in cord blood leukocytes (CBL) and adult blood leukocytes (ABL) by various stimuli. Results: While interleukin-2 (IL-2) levels were similar in CBL and ABL, there was less induction of the Th1 cytokine interferon-γ in CBL. Production of the Th2 cytokines IL-4, IL-5, and IL-13 and the hematopoietic cytokine IL-3 was much lower in CBL versus ABL after T-cell receptor-mediated stimulation, whereas production of GM-CSF was comparable in the 2 cell types. The lower levels of Th1 and Th2 cytokines were maintained in CBL during a 4-day time-course study, while after 12 hours IL-3 and GM-CSF reached in CBL levels similar to those in ABL. For all cytokines except IFNγ, the IC50 values for inhibition by cyclosporin A were similar in ABL and CBL. In contrast, there was less expression and activation of transcription factors in CBL. Activation of NF-κB by TPA/ ionomycin was detected in ABL but not CBL. Furthermore, there was less expression of the Th subset-specific transcription factors T-bet and c-maf in CBL versus ABL, whereas GATA-3 expression was similar. Expression of T-bet and c-maf correlated with expression of the Th1 and Th2 cytokines, respectively. Time course experiments revealed that T-bet expression was stimulated in both cell types, whereas c-maf and GATA-3 were induced only in ABL. Conclusion: The diminished capability of CBL to synthesize cytokines is probably due to decreased activation of NF-κB, whereas differences in Th subsets are due to differences in regulation of Th lineage-specific transcriptions factors. We propose that the reduced incidence and severity of GvHD after allogeneic transplantation of umbilical CB cells is due to lesser activation of specific transcription factors and a subsequent reduction in production of certain cytokines.ger
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectAdulteng
dc.subjectHumanseng
dc.subjectAntigenseng
dc.subjectFemaleeng
dc.subjectMaleeng
dc.subjectMiddle Agedeng
dc.subjectRNAeng
dc.subjectSurface/metabolismeng
dc.subjectCyclosporine/pharmacologyeng
dc.subjectCytokines/biosynthesiseng
dc.subjectCytokines/geneticseng
dc.subjectFetal Blood/drug effectseng
dc.subjectFetal Blood/metabolism*eng
dc.subjectGene Expression Regulation*/drug effectseng
dc.subjectHematopoiesis/drug effectseng
dc.subjectInhibitory Concentration 50eng
dc.subjectKineticseng
dc.subjectLeukocytes/drug effectseng
dc.subjectLeukocytes/metabolismeng
dc.subjectMessenger/geneticseng
dc.subjectMessenger/metabolismeng
dc.subjectTetradecanoylphorbol Acetate/pharmacologyeng
dc.subjectTh1 Cells/drug effectseng
dc.subjectTh1 Cells/metabolismeng
dc.subjectTh2 Cells/drug effectseng
dc.subjectTh2 Cells/metabolismeng
dc.subjectTranscription Factors/geneticseng
dc.subjectTranscription Factors/metabolismeng
dc.subject.ddc610 Medizin
dc.titleCytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-1006203
dc.identifier.doi10.1186/1471-2172-8-18
dc.identifier.doihttp://dx.doi.org/10.25646/535
local.edoc.container-titleBMC Immunology
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.biomedcentral.com/1471-2172/8/18/abstract
local.edoc.container-publisher-nameBioMedCentral
local.edoc.container-volume8
local.edoc.container-issue18
local.edoc.container-year2007

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