Mechanistic Insights into Necroptosis of Macrophages

FieldValue
dc.contributor.authorCessford, Erin Lauren
dc.date.accessioned2014-10-31T17:05:35Z
dc.date.available2014-10-31T17:05:35Z
dc.date.created2014
dc.date.issued2014
dc.identifier.urihttp://hdl.handle.net/10393/31771
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-6651
dc.description.abstractCell death is an imperative mechanism for the development, homeostasis and survival of an organism. Various forms of cell death have been documented and recent reports indicate that the mode of cell death elicited can have a profound influence on the development and perpetuation of inflammation. Apoptosis is the predominant, programmed pathway of cell death, which ensures physiological elimination of unwanted cells. On the other hand, another cell death pathway described as programmed necrosis (necroptosis), has recently been revealed. The induction of necroptosis and its impact in host biology is not clear. Herein I have evaluated the mechanisms of necroptosis in macrophages, an important cell type of the immune system. My experiments indicate that type I interferon (IFN-I) signaling through transcription factors STAT1, STAT2 and IRF9, collectively described as the ISGF3 complex, is indispensable for necroptosis of macrophages. Furthermore, my results indicate that IFN-I signaling promotes the sustained phosphorylation of receptor interacting protein kinase 3 (Rip3), a key protein required for the execution of necroptosis. My findings also reveal that dynamin-dependent endocytosis following IFNβ stimulation and caspase inhibition is necessary for the induction of necroptosis. The results presented in this thesis provide new insights into the molecular mechanisms of necroptosis and therefore contribute to a deeper understanding of multiple inflammatory pathologies.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectCell Death
dc.subjectNecroptosis
dc.subjectMacrophages
dc.subjectInflammation
dc.subjectInnate Immunity
dc.subjectType I Interferons
dc.titleMechanistic Insights into Necroptosis of Macrophages
dc.typeThesis
dc.faculty.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
dc.contributor.supervisorSad, Subash
dc.degree.nameMSc
dc.degree.levelmasters
dc.degree.disciplineMédecine / Medicine
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
CollectionThèses, 2011 - // Theses, 2011 -

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