Örebro Studies in Medicine 227 I
ÖREBRO 2021 ÖREBRO STUDIES IN MEDICINE 227 2021M
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mulugeta melkie zegeye graduated with Bachelor of Science Degree in Medical Laboratory Technology from University of Gondar (Ethiopia) in 2007. He received Master of Science Degree in Clinical Chemistry from Addis Ababa University (Ethiopia) in 2011. In 2014, Mulugeta moved to Sweden to study Master of Science in Biomedicine-Experimental Medicine at Cardiovascular Research Centre (CVRC), Örebro University. He continued his PhD studies in the same research environment since 2016.
Interlekin-6 (IL-6) is a pleotropic cytokine that is produced by several types of cells including immune cells and non-immune cells. It plays wide array of functions including homeostatic or anti-inflammatory activities to pro-inflammatory activities. These dual roles of IL-6 appear to originate from how IL-6 interacts with a specific target cell. IL-6 engages target cells via two major signaling mechanisms known as classic signaling and trans-signaling where classic signaling mediates homeostatic or anti-inflammatory activities while the trans-signaling is linked to pro-inflammatory activities that have been associated with chronic inflammatory diseases. This thesis sheds light on molecular differences of IL-6 signaling pathways in human vascular endothelial cells in terms of intracellular signaling pathways, downstream proteomic and transcriptomic regulations on soluble and basement proteins, and endothelial functions such as migration, proliferation and tube forma-tion. In addition, this thesis addresses the link between IL-6 trans-signaling to atherosclerosis and risk factors of myocardial infarction (MI) using a novel biomarker estimated from plasma concentration of IL-6, sIL-6R and sgp130.
issn 1652-4063 isbn 978-91-7529-366-0