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dc.contributor.advisorStevenson, Nigel
dc.contributor.authorALMOHAMMADI, DANIAH HAMEED
dc.date.accessioned2020-05-07T15:48:42Z
dc.date.available2020-05-07T15:48:42Z
dc.date.issued2020en
dc.date.submitted2020
dc.identifier.citationALMOHAMMADI, DANIAH HAMEED, A novel role of SOCS-4 and SOCS-5 in cytokine signalling, Trinity College Dublin.School of Biochemistry & Immunology, 2020en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/92465
dc.descriptionAPPROVEDen
dc.description.abstractThe immune system is propagated by cytokines and their intracellular signal transduction. To ensure an appropriate immune response, these signalling pathways are tightly controlled. One such regulatory mechanism is the induction of a family of 8 intracellular proteins called Suppressor of Cytokine Signalling (CIS [Cytokine-inducible SH2 protein] and SOCS1-7). Many cytokines and pathogenic stimuli have been shown to regulate SOCS expression, which subsequently act by binding to components of the intracellular pathway and thus block the cascade of signalling events. CIS, SOCS1-3 are the most comprehensively described SOCS proteins, with SOCS4-7 being less well understood. Therefore, this project aimed to investigate the role of 2 of these 'neglected SOCS', SOCS4 and SOCS5 and their involvement in the signal transduction of pro-inflammatory (TNF-α, IL-6 and IL-1β) and anti-viral (IFN-) cytokines. Indeed, we discovered that both SOCS4 and SOCS5 mRNA and expression were induced by these cytokines, to varying degrees. Interestingly, while SOCS4 overexpression inhibited IL-6-mediated STAT3 phosphorylation, SOCS5 expression enhanced IL-6-mediated pSTAT3 levels. However, SOCS5 expression acted to reduce TNF-α-mediated IκBα degradation. Together these findings reveal for the first time, that both SOCS4 and SOCS5 are induced by pro-inflammatory and anti-viral cytokines and that SOCS5 can regulate pro-inflammatory signalling of both IL-6 and TNF-, and while SOCS4 has no inhibitory effect upon TNF- signaling, it acts to reduce pro-inflammatory responses of IL-6. These discoveries have not only revealed that SOCS4 and SOCS5 expression are regulated, but have shed light upon new immune regulatory mechanisms for both of these proteins.en
dc.language.isoenen
dc.publisherTrinity College Dublin. School of Biochemistry & Immunology. Discipline of Biochemistryen
dc.rightsYen
dc.subjectSOCS4en
dc.subjectSOCS5en
dc.titleA novel role of SOCS-4 and SOCS-5 in cytokine signallingen
dc.typeThesisen
dc.type.supercollectionthesis_dissertationsen
dc.type.supercollectionrefereed_publicationsen
dc.type.qualificationlevelMasters (Research)en
dc.identifier.peoplefinderurlhttps://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:ALMOHAMDen
dc.identifier.rssinternalid216226en
dc.rights.ecaccessrightsopenAccess
dc.rights.restrictedAccessY
dc.date.restrictedAccessEndDate2021-05-07
dc.contributor.sponsorThe government of Saudi Arabia scholarship programen


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