Molecular mechanism for adenosine regulation of dendritic cells

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buir.advisorÇekiç, Çağlar
dc.contributor.authorKayhan, Merve
dc.date.accessioned2017-06-06T10:48:52Z
dc.date.available2017-06-06T10:48:52Z
dc.date.copyright2017-05
dc.date.issued2017-05
dc.date.submitted2017-06-05
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2017.en_US
dc.descriptionIncludes bibliographical references (leaves 56-68).en_US
dc.description.abstractCell death, inflammation or other cellular stress factors cause accumulation of adenosine in the extracellular space. Adenosine has immunosuppressive effects on antigen presenting cells. However, molecular mechanisms for adenosine regulation of dendritic cells are poorly understood. Here we showed that adenosine receptor signaling promotes an antiinflammatory dendritic cell phenotype. While adenosine receptor signaling increased intracellular cAMP levels, phosphoactivation of major inflammatory pathways such as MAPKs, NF-κB and IRF3 were not affected. Adenosine’s effects were phenocopied by cAMP. Specific cAMP analogs for EPAC and PKA pathways indicated that adenosine activates both intracellular cAMP receptors to inhibit dendritic cell activation. Antiinflammatory cFOS and NR4A receptor family expressions were increased by adenosine or EPAC and PKA specific cAMP analogs. Furthermore, T cells incubated with the medium of dendritic cells, which prestimulated with adenosine receptor agonist and PKAEPAC specific cAMP analogs, produced less IFNγ. Overall our data suggest that dendritic cells are regulated by adenosine through both PKA and EPAC pathways and increased the expression of NR4A nuclear orphan receptors and cFOS. Our findings suggest that for effective targeting of adenosine or other cAMP-inducing receptors both PKA and EPAC are important to modulate immune responsesen_US
dc.description.degreeM.S.en_US
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2017-06-06T10:48:52Z No. of bitstreams: 1 10149608.pdf: 5001746 bytes, checksum: f3d645f011a50d85a7b1de0fb089d9f3 (MD5)en
dc.description.provenanceMade available in DSpace on 2017-06-06T10:48:52Z (GMT). No. of bitstreams: 1 10149608.pdf: 5001746 bytes, checksum: f3d645f011a50d85a7b1de0fb089d9f3 (MD5) Previous issue date: 2017-06en
dc.description.statementofresponsibilityby Merve Kayhan.en_US
dc.embargo.release2020-06-05
dc.format.extentxvii, 82 leaves : charts (some color) ; 29 cmen_US
dc.identifier.itemidB155687
dc.identifier.urihttp://hdl.handle.net/11693/33191
dc.language.isoEnglishen_US
dc.publisherBilkent Universityen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAdenosine receptorsen_US
dc.subjectcAMP signalingen_US
dc.subjectPKAen_US
dc.subjectEPACen_US
dc.subjectDendritic cellsen_US
dc.titleMolecular mechanism for adenosine regulation of dendritic cellsen_US
dc.title.alternativeAdenozinin dendritik hücreler üzerindeki etkilerinin moleküler mekanizmasıen_US
dc.typeThesisen_US

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