Suppressive oligodeoxynucleotides as a TLR antagonist : efforts to treat autoimmune diseases

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buir.advisorGürsel, İhsan
dc.contributor.authorYağcı, Fuat Cem
dc.date.accessioned2016-01-08T18:02:30Z
dc.date.available2016-01-08T18:02:30Z
dc.date.issued2007
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent Univ., 2007.en_US
dc.descriptionThesis (Master's) -- Bilkent University, 2007.en_US
dc.descriptionIncludes bibliographical references leaves 51-59.en_US
dc.description.abstractSynthetic oligodeoxynucleotides (ODN) expressing suppressive TTAGGG motifs effectively down-regulate the production of proinflammatory and Th1 cytokines elicited by a variety of Toll-Like Receptor (TLR) dependent or independent immune stimuli. Although initially identified by their ability to block CpG-induced immune activation, this class of suppressive ODN (typified by ODN A151) was subsequently shown to block multiple forms of immune stimulation and to be effective in the prevention and treatment of pathologic autoimmune diseases. Endotoxin-induced uveitis (EIU) is an established animal model of acute ocular inflammation. It is induced by either systemic or intravitreal administration of lipopolysaccharide (LPS). FMF is an autosomal recessive periodic fever disease characterized by recurrent, self-limiting, febrile, inflammatory attacks of the serosal membranes such as peritoneum, pleura, and synovia. FMF patients in clinical remission are reported to have increased baseline inflammation. Present study aims to demonstrate that the downregulatory effect of the suppressive DNA could prove benefit to alleviate the symptoms associated with i) LPS induced EIU in rabbit or murine models as model for local autoimmune disease and ii) Familial Mediterranean Fever a model for systemic autoinflammatory disease. Results from this research strongly implicated that A151 treated EIU induced animals downregulated IL6 and IL1b cytokine secretion or expression as well as chemokines such as or MIP3a, or iNOS levels. Our data suggest that FMF patient PBMCs to that of healthy donor`s blood were more responsive to TLR ligand stimulation and A151 incubation strongly reversed this activation and suppressed certain key cytokine/chemokine levels.en_US
dc.description.provenanceMade available in DSpace on 2016-01-08T18:02:30Z (GMT). No. of bitstreams: 1 0003415.pdf: 1427419 bytes, checksum: 7cfb775875784566df05d1d66cba77ce (MD5)en
dc.description.statementofresponsibilityYağcı, Fuat Cemen_US
dc.format.extentxiv, 61 leaves, tablesen_US
dc.identifier.urihttp://hdl.handle.net/11693/14582
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectSuppressive DNAen_US
dc.subjectantagonizmen_US
dc.subjectTLRen_US
dc.subjectimmunoregulatory effecten_US
dc.subjectautoimmunityen_US
dc.subject.lccQD435 .Y34 2007en_US
dc.subject.lcshDNAen_US
dc.subject.lcshNucleic acids.en_US
dc.subject.lcshAutoimmune diseases.en_US
dc.subject.lcshAutoimmunity.en_US
dc.titleSuppressive oligodeoxynucleotides as a TLR antagonist : efforts to treat autoimmune diseasesen_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelMaster's
thesis.degree.nameMS (Master of Science)

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