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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/24881

Title: The Role of TIMP3 in Models of Inflammation and Immunity
Authors: Smookler, David
Advisor: Khokha, Rama
Department: Laboratory Medicine and Pathobiology
Keywords: TIMP3
MMP
TNF
LPS
Issue Date: 1-Sep-2010
Abstract: The inter-relation between inflammation, the immune system and leukocytes is multifaceted, with communication between stroma and immune cells mediated by cytokines, growth factors, chemokines, integrins and other molecules. Proteolysis plays an important role in regulating these molecules. Proteolytic cleavage can not only destroy some molecules but can activate or shed others, converting local juxtacrine signalling proteins into effectors that act at a distance. Shedding can also convert membrane-bound receptors into soluble ligand-binding inhibitors. Finally, cleavage can convert agonist molecules into antagonists. As a wide-ranging inhibitor of metalloproteinases, tissue inhibitor of metalloproteinase 3 (TIMP3) has the potential to down-regulate many of these activities. We explore the role of TIMP3 in the regulation of inflammation, revealing that loss of TIMP3 leads to a more rapid increase of soluble TNF, higher levels of soluble TNF receptors and ultimately to increased TNF signalling in systemic inflammation. We also demonstrate TIMP3 loss impacts local inflammation. In addition we investigate the importance of TIMP3 in the expansion of hematopoietic cells.
URI: http://hdl.handle.net/1807/24881
Appears in Collections:Doctoral
Department of Laboratory Medicine and Pathobiology - Doctoral theses

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