Date of Award
2008
Degree Type
Thesis
Degree Name
Master of Science
Program
Microbiology and Immunology
Supervisor
Dr. Anthony Jevnikar
Second Advisor
Dr. Bhagirath Singh
Third Advisor
Dr. Ewa Cairns
Abstract
Human serpin protease inhibitor 9 (PI-9) inhibits Granzyme B (GrB) function. However, its role in protection from renal injury is unknown. Tubular epithelial cells (TEC) express serine protease inhibitor 6 (SPI-6), the murine homolog of human PI-9. SPI-6 protein expression increased in response to IFNγ or LPS and detachment stress. This occurred without increased mRNA expression suggesting SPI-6 is post transcriptionally regulated. Cloned TEC were resistant to GrB killing. However in SPI-6 gene silenced TEC, death significantly increased from baseline levels (10.7% + 2.4 to 21.22% + 1, p= 0.0002) when assessed by Annexin V∕7AAD. Kidney SPI-6 protein expression by immuno-histochemistry and western blotting, increased in TEC in vivo following ischemia-reperfusion injury (IRI). Expression of SPI-6 by TEC may provide protection from GrB producing cytotoxic CD8+T and NK cells, which are involved in IRI and rejection. Therefore, augmenting or maintaining SPI-6∕PI-9 expression by TEC may promote long term allograft survival.
Recommended Citation
Khan, Karim, "Serpin Protease Inhibitors and Endogenous Resistance of Tubular Epithelial Cells to Granzyme B Injury" (2008). Digitized Theses. 4723.
https://ir.lib.uwo.ca/digitizedtheses/4723