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dc.provenanceFacultad de Ciencias Exactas y Naturales de la UBA-
dc.contributor<div class="autor_fcen" id="4984">Liberman, A.C.</div>-
dc.contributorAntunica-Noguerol, M.-
dc.contributorFerraz-de-Paula, V.-
dc.contributorPalermo-Neto, J.-
dc.contributor<div class="autor_fcen" id="1656">Castro, C.N.</div>-
dc.contributor<div class="autor_fcen" id="2675">Druker, J.</div>-
dc.contributorHolsboer, F.-
dc.contributorPerone, M.J.-
dc.contributorGerlo, S.-
dc.contributorde Bosscher, K.-
dc.contributorHaegeman, G.-
dc.contributorArzt, E.-
dc.creator<div class="autor_fcen" id="4984">Liberman, A.C.</div>-
dc.creatorAntunica-Noguerol, M.-
dc.creatorFerraz-de-Paula, V.-
dc.creatorPalermo-Neto, J.-
dc.creator<div class="autor_fcen" id="1656">Castro, C.N.</div>-
dc.creator<div class="autor_fcen" id="2675">Druker, J.</div>-
dc.creatorHolsboer, F.-
dc.creatorPerone, M.J.-
dc.creatorGerlo, S.-
dc.creatorde Bosscher, K.-
dc.creatorHaegeman, G.-
dc.creatorArzt, E.-
dc.date.accessioned2018-05-04T22:04:30Z-
dc.date.accessioned2018-05-28T15:49:17Z-
dc.date.available2018-05-04T22:04:30Z-
dc.date.available2018-05-28T15:49:17Z-
dc.date.issued2012-
dc.identifier.urihttp://10.0.0.11:8080/jspui/handle/bnmm/68626-
dc.descriptionBackground: Compound A (CpdA) is a dissociating non-steroidal glucocorticoid receptor (GR) ligand which has anti-inflammatory properties exerted by down-modulating proinflammatory gene expression. By favouring GR monomer formation, CpdA does not enhance glucocorticoid (GC) response element-driven gene expression, resulting in a reduced side effect profile as compared to GCs. Considering the importance of Th1/Th2 balance in the final outcome of immune and inflammatory responses, we analyzed how selective GR modulation differentially regulates the activity of T-bet and GATA-3, master drivers of Th1 and Th2 differentiation, respectively. Results: Using Western analysis and reporter gene assays, we show in murine T cells that, similar to GCs, CpdA inhibits T-bet activity via a transrepressive mechanism. Different from GCs, CpdA induces GATA-3 activity by p38 MAPK-induction of GATA-3 phosphorylation and nuclear translocation. CpdA effects are reversed by the GR antagonist RU38486, proving the involvement of GR in these actions. ELISA assays demonstrate that modulation of T-bet and GATA-3 impacts on cytokine production shown by a decrease in IFN-γ and an increase in IL-5 production, respectively. Conclusions: Taken together, through their effect favoring Th2 over Th1 responses, particular dissociated GR ligands, for which CpdA represents a paradigm, hold potential for the application in Th1-mediated immune disorders. © 2012 Liberman et al.-
dc.descriptionFil:Liberman, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.descriptionFil:Castro, C.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.descriptionFil:Druker, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.-
dc.formatapplication/pdf-
dc.languageeng-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttp://creativecommons.org/licenses/by/2.5/ar-
dc.sourcePLoS ONE 2012;7(4)-
dc.source.urihttp://digital.bl.fcen.uba.ar/Download/paper/paper_19326203_v7_n4_p_Liberman.pdf-
dc.subjectcompound A-
dc.subjectdexamethasone-
dc.subjectgamma interferon-
dc.subjectglucocorticoid receptor-
dc.subjectinterleukin 5-
dc.subjectmifepristone-
dc.subjecttranscription factor GATA 3-
dc.subjectunclassified drug-
dc.subject2 (4 acetoxyphenyl) 2 chloro N methyl ethylammonium chloride-
dc.subject2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride-
dc.subjectaziridine derivative-
dc.subjectgamma interferon-
dc.subjectGata3 protein, mouse-
dc.subjectglucocorticoid receptor-
dc.subjectmifepristone-
dc.subjectquaternary ammonium derivative-
dc.subjectT box transcription factor-
dc.subjectT box transcription factor TBX21-
dc.subjectT-box transcription factor TBX21-
dc.subjecttranscription factor GATA 3-
dc.subjectanimal cell-
dc.subjectarticle-
dc.subjectcell differentiation-
dc.subjectcontrolled study-
dc.subjectcytokine production-
dc.subjectdimerization-
dc.subjectenzyme linked immunosorbent assay-
dc.subjectgene expression-
dc.subjectimmune response-
dc.subjectimmunocompetent cell-
dc.subjectligand binding-
dc.subjectmouse-
dc.subjectnonhuman-
dc.subjectprotein expression-
dc.subjectprotein phosphorylation-
dc.subjectreporter gene-
dc.subjectspleen cell-
dc.subjectTh1 cell-
dc.subjectTh2 cell-
dc.subjectanimal-
dc.subjectBagg albino mouse-
dc.subjectbiosynthesis-
dc.subjectdrug antagonism-
dc.subjectdrug effect-
dc.subjectdrug potentiation-
dc.subjectimmunology-
dc.subjectspleen-
dc.subjectT lymphocyte-
dc.subjectTh1 Th2 balance-
dc.subjectMurinae-
dc.subjectAnimals-
dc.subjectAziridines-
dc.subjectGATA3 Transcription Factor-
dc.subjectInterferon-gamma-
dc.subjectMice-
dc.subjectMice, Inbred BALB C-
dc.subjectMifepristone-
dc.subjectQuaternary Ammonium Compounds-
dc.subjectReceptors, Glucocorticoid-
dc.subjectSpleen-
dc.subjectT-Box Domain Proteins-
dc.subjectT-Lymphocytes-
dc.subjectTh1 Cells-
dc.subjectTh1-Th2 Balance-
dc.subjectTh2 Cells-
dc.titleCompound a, a dissociated glucocorticoid receptor modulator, inhibits t-bet (th1) and induces gata-3 (th2) activity in immune cells-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:ar-repo/semantics/artículo-
dc.typeinfo:eu-repo/semantics/publishedVersion-
Aparece en las colecciones: FCEN - Facultad de Ciencias Exactas y Naturales. UBA

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