Effects of Interleukin-17 on Endothelial Nitric Oxide Synthase and Transplant Arteriosclerosis

Author: 
Date created: 
2014-09-30
Identifier: 
etd8721
Keywords: 
Transplantation
Transplant arteriosclerosis
T helper 17
Interleukin-17
Endothelial nitric oxide synthase
Nitric oxide
Abstract: 

Transplant arteriosclerosis (TA), a vascular condition characterized by intimal thickening and vasomotor dysfunction of allograft arteries, is a leading cause of solid organ transplant failure. Properties of the endothelium such as the activity of eNOS control the structural and functional changes that occur in arteries with TA. We have examined the effect of IL-17 on eNOS expression in endothelial cells. Up-regulation of eNOS by IL-17 occurred through a post-translational mechanism because there was no effect of IL-17 on eNOS mRNA levels and inhibition of mRNA translation with cycloheximide did not prevent eNOS induction; but IL-17 treatment of ECs prolonged eNOS protein half-life. To begin examining the role of IL-17 signaling in graft cells in the development of TA, aortic segments from WT and IL-17RA-KO mice were interposed into allogeneic recipients. There were no significant changes in terms of TA development in IL-17RA-KO transplants compared to WT transplants. In summary, these results begin to define the cellular mechanisms by which IL-17 induces eNOS and the relevance of this cytokine to the pathogenesis of TA.

Document type: 
Thesis
Rights: 
Copyright remains with the author. The author granted permission for the file to be printed and for the text to be copied and pasted.
File(s): 
Supervisor(s): 
Jonathan Choy
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.
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