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Title: The Expression and Cellular Function of NOD2
Author: Wakenshaw, Louise
ISNI:       0000 0001 3550 9948
Awarding Body: The University of Leeds
Current Institution: University of Leeds
Date of Award: 2007
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The gastrointestinal mucosa is composed of an epithelial cell barrier .' with underlying lamina propria and muscle lay.~Js, these function together to '. form a wall which can be inhabited by commensal bacteria yet '. act as a barrier to protect against pathogenic or opportunistic organisms. One of the most important featu~es maintaining this defensive barrier is the constant turnover of epithelial cells and wou.nd repair mechanisms. In the event of damage to the wall cytoprotective factors, such as IL-6 and growth factors are released, stimulating· rapid proliferation and wound repair of the epithelium. This study has identified a novel function for the cytosolic pattern . . recognition receptor, Nucleotide oligomerisation domain 2 (NOD2), in the regulation of colonic epithelial cell turnover. WT'and NOD2-deficient mice prior to and in response to infection with the bacterium, S.typhimurium demonstrated reduced proliferation and increased susceptibility to apoptosis in vivo. RNA .interference of NOD2 in vitro confirmed dysregulated CEC homeostasis in the absence of NOD2. CEC homeostasis could in part be regulated by the secretion of IL-6, a cytoprotective factor, from CECs, as. demonstrated by the protection of CEC apoptosis when cultured in the presence of recombinant IL-6. In conclusion, this data identifies ~ role for NOD2 in the maintainance ... of the mucosal barrier. This provides reasoning for why loss of function NOD2 mutations enhance susceptibility to the. development of the inflammatory bowel disease, Crohn's.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available