Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.578079
Title: Functional analysis of the G-protein coupled chemokine receptor CXCR3-A and its ligands
Author: Rahman, Ishrat
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2007
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Abstract:
CXCR3 is a G-protein coupled chemokine receptor. Chemokine receptors play a key part in orchestrating immune responses. CXCR3 in particular has attracted attention owing to its abundant expression in activated T-cells and its role in the trafficking of Thl cells to sites of inflammation, and thus may potentially be involved in the pathogenesis of many chronic inflammatory diseases, such as Multiple Sclerosis (MS) and Rheumatoid arthritis (RA). CXCR3 is known to exist as two functional variants; CXCR3-A and CXCR3-B, both associated with diverse signalling events and exert contrasting functional effects. This thesis explores the effect of T -cell activation on CXCR3 expression and compares the agonist induced CXCR3-A signalling events in CHO-CXCR3-A cells and activated T-cells. T -cell activation causes a two-phase mechanism of CXCR3 induction to occur in CD4+ T- cells. Transcriptional regulation of the CXCR3 gene occurs in naive CD4+ T -cells early in activation (days I to 4), to down-regulate CXCR3-B and up-regulate CXCR3-A mRNA. During mid-activation (days 4 to 8) these cells become high CXCR3-A expressing mature Thl effector cells (CD4+CXCR3-A+high T-cells) but become low in frequency. CD4+CXCR3-A+high T-cells may be implicated in the pathogenesis of Thl type chronic disorders as they constitutively express high levels of CXCR3-A, which is known to be a tissue homing chemokine receptor. A comparative study of the agonist induced pharmacological response of CXCR3-A in CHO-CXCR3-A transfected cells and in activated T -cells shows that T -cells may be a better system to study CXCR3-A signalling in and differences in signalling events seem to arise due to changes in cell environment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.578079  DOI: Not available
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