IL-15 is a pleiotropic cytokine which influences a variety of immune and inflammatory responses. Our lab has previously demonstrated that IL-15 and IL-15Rα promote atherosclerosis. However, the mechanisms by which IL-15 affect atherosclerosis development were not fully defined. In this study, we reported that overexpression of the IL-15 gene resulted in an increase of granzyme B level in the atherosclerotic plaque of ApoE deficient mice. Furthermore, we observed that leukocytes-specific genetic deletion of IL-15Rα reduced the granzyme B level within atherosclerotic lesions from LDLr deficient mice. Collectively, our data shows one of the mechanistic pathways by which IL-15 promotes atherosclerosis development.
Moreover, we tested the role of IL-15 in carotid artery disease. It has been reported previously that immunization of low density lipoprotein receptor deficient mice against IL-15, by inoculating them with bacteria harboring an IL-15 expression plasmid, led to reduced development of diet induced atherosclerosis in carotid arteries whose diameter was restricted to induce a hemodynamic stress. Others, however, reported that injection of wild type mice with an antibody against IL-15 triggered increased neointima formation in carotid arteries that were partially ligated. In our study, we found no differences in the amount of collar/diet induced atherosclerosis in control apoE KO mice and in IL-15/apoE dKO mice.Therefore,inactivation of IL-15 gene expression does not appear to affect the rapid onset of atherosclerosis in carotid arteries of ApoE KO mice induced by a combination of high fat diet and hemodynamic stress. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/19142 |
| Date | January 2016 |
| Creators | Alshuweishi, Yazeed |
| Contributors | Trigatti, Bernardo, Biochemistry and Biomedical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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