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Title: The immunomodulatory role of proteinase activated receptor-2 (PAR-2) in B cells
Author: Campbell, Michelle
Awarding Body: University of the West of Scotland
Current Institution: University of the West of Scotland
Date of Award: 2013
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Proteinase activated receptor-2 (PAR-2) is a seven transmembrane G protein coupled receptor (GPCR) which is activated by proteolytic cleavage to reveal a cryptic tethered ligand (Macfarlane et al, 2001). Whilst PAR-2 expression has been demonstrated in a number of immune related cells (Shpacovitch et al, 2008) and has been shown on human synovial B cells (Busso et al, 2007) however a functional role for the receptor has not been proposed. Previous studies have demonstrated the benefit of PAR-2 antagonism in inflammatory models. Utilising the antagonist ENMD-1068 as a treatment in the collagen induced arthritis (CIA) model resulted in the reduction of clinical disease severity as well as reducing the proportion of splenic B cells compared with vehicle treated mice. PAR-2 was shown to be expressed on B cell progenitors, splenic, bone marrow and peritoneal B cell subsets. Following induction of CIA this expression was up-regulated in the bone marrow Hardy fraction progenitor cells, and the innate like B cell subsets found in the peritoneum, spleen and bone marrow, consistent with up-regulated PAR-2 expression found on T cells and monocytes from patients with rheumatoid arthritis (Crilly et al, 2012b).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available