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dc.contributor.advisorGanea, Doina
dc.creatorKocieda, Virginia Polonia
dc.date.accessioned2020-10-27T15:13:57Z
dc.date.available2020-10-27T15:13:57Z
dc.date.issued2013
dc.identifier.other864885914
dc.identifier.urihttp://hdl.handle.net/20.500.12613/1644
dc.description.abstractWe reported previously that prostaglandin E2 (PGE2) upregulates IL-23 in vitro in bone marrow-derived dendritic cells (DC), and in vivo in models of collagen-induced arthritis and inflammatory bowel disease, leading to preferential Th17 development and activity. There is very little information on the molecular mechanisms involved in the PGE2-induced upregulation of Il23a gene expression. In the present study we investigated the signaling pathways and transcription factors involved in the stimulatory effect of PGE2. Although PGE2 does not induce IL-23p19 expression by itself, it synergizes with both extra- and intracellular TLR ligands and with inflammatory cytokines such as TNFα. We established that the effect of PGE2 in conjunction with either LPS or TNFα is mediated through the EP4 receptor and the cAMP-dependent activation of both PKA and EPAC. Using the EP4 agonist PGE1OH in conjunction with TNFα, we found that PKA-induced PCREB and EPAC-induced PC/EBPβ mediate the stimulatory effect of PGE2 on IL-23p19 expression. This is the first report of CREB and C/EBPβ involvement in Il23a promoter activation. Mutation within the putative CREB and C/EBP sites combined with in vivo DNA binding (ChIP) assays identified the distal CREB site (-1125) and the two proximal C/EBP sites (-274 and -232) as essential for PKA-activated CREB and EPAC-activated C/EBPβ induced IL-23p19 expression.
dc.format.extent136 pages
dc.language.isoeng
dc.publisherTemple University. Libraries
dc.relation.ispartofTheses and Dissertations
dc.rightsIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectImmunology
dc.subjectBiology, Molecular
dc.subjectC/ebp
dc.subjectCreb
dc.subjectDendritic Cell
dc.subjectIl-23
dc.subjectPge2
dc.titleProstaglandin E2-induced IL-23p19 is regulated by CREB and C/EBP beta in bone marrow derived dendritic cells
dc.typeText
dc.type.genreThesis/Dissertation
dc.contributor.committeememberMonestier, Marc
dc.contributor.committeememberTsygankov, Alexander Y.
dc.contributor.committeememberPraticò, Domenico
dc.contributor.committeememberGamero, Ana
dc.description.departmentMicrobiology and Immunology
dc.relation.doihttp://dx.doi.org/10.34944/dspace/1626
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.degreePh.D.
refterms.dateFOA2020-10-27T15:13:57Z


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