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Title: An investigation of inflammatory responses and wound healing in heat shock protein B1-deficient mice
Author: Crowe, Jonathan
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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The function of heat shock protein B1 (hspB1) in vivo is still poorly understood, despite a large literature describing in vitro functions of the protein. This research has focussed on the role of hspB1 in vivo, an opportunity created by the commercial generation of hspB1-deficient mice (hspB1del/del). Initial experiments demonstrated an increase in cytokine production in hspB1del/del murine embryonic fibroblasts. Two well established and characterised in vivo models of acute inflammation, the air-pouch model and the peritonitis model, were used to investigate the role of hspB1. Increased cellular infiltration and an increase in chemokine expression in response to inflammatory challenge was observed in hspB1del/del mice relative to wild-type mice. It was found that the majority of the cellular infiltrate consisted of neutrophils, and these cells had reduced viability in hspB1del/del mice compared to wild-type mice, despite the discovery that neither hspB1 protein or mRNA could be detected in murine neutrophils. The work of Anna Aubareda, a post-doc in the laboratory, showed that hspB1-deficiency results in impaired cell proliferation. The observation of a phenotype of increased inflammation and decreased proliferation in hspB1del/del mice and cells led to an investigation into the role of hspB1 in wound-healing. It was discovered that hspB1del/del mice have significantly impaired healing in response to excisional wounding compared to wild-type mice. HspB1 protein expression is increased in the proliferating epithelium of wounds in wild-type mice. It was also shown that hspB1 deficiency results in increased chemokine production and neutrophil accumulation within in wounds. This research proposes an important role for hspB1 in inflammatory responses and wound healing in vivo.
Supervisor: Dean, Jonathan Sponsor: Arthritis Research UK ; Kennedy Institute of Rheumatology
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available