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The effect of interferon-gama and interleukin-15, -20, -22 and -37 on macrophage gene expression and uptake of modified low-density lipoprotein in relation to atherosclerosis.

Altuwayjiri, Hadeel 2012. The effect of interferon-gama and interleukin-15, -20, -22 and -37 on macrophage gene expression and uptake of modified low-density lipoprotein in relation to atherosclerosis. MPhil Thesis, Cardiff University.
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Abstract

Atherosclerosis, a chronic inflammatory disorder of the vasculature, is the underlying cause of heart attacks and stroke and responsible for most deaths in western society. A range of cytokines regulates the initiation, progression and clinical complications of atherosclerosis and affects all the cell types present in a lesion. Macrophages play an important role in all stages of the disease from the uptake of modified lipoproteins to amplification of the inflammatory response to plaque rupture. Because of the key roles of cytokines in atherosclerosis, it is important that their effects on macrophage properties and gene expression are fully understood. Although the action of classical cytokines, such as interferon-γ (IFN-γ), on macrophages and atherosclerosis is well understood, this is not the case with those that have been more recently identified such as interleukin (IL)-15, -20, -22 and -37. The aim of this study was therefore to investigate the effect of these cytokines using human THP-1 macrophages and mouse RAW264.7 macrophages as model systems. The action of IFN-γ was used as a positive control. Real-time quantitative polymerase chain reaction showed that IFN-γ induced the mRNA expression of two markers of inflammation, monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1), in THP-1 macrophages. From the other cytokines analysed, IL-20, IL-22 and IL-37 had no effect on the expression of these genes. In contrast, IL-15 inhibited the mRNA expression of both MCP-1 and ICAM-1. Western blot analysis indicated that the changes in ICAM-1 mRNA expression by IFN-γ and IL-15 were accompanied by corresponding changes at the level of the protein. Initial experiments on the effect of IFN-γ or IL-15 on the uptake of modified low-density lipoprotein by THP-1 macrophages were also carried out though firm conclusions could not be made and further optimisation will be required. The effect of IL-15 on MCP-1 mRNA expression in human THP-1 macrophages contrasted with a previous study that showed induced expression in mouse RAW264.7 macrophages. Experiments in these cells indeed showed that IL-15 induced the mRNA expression of MCP-1, and also ICAM-1. The studies provide new insight into the action of recently identified cytokines on macrophage gene expression and suggest the potential existence of species-specific effects of IL-15 that needs to be further investigated.

Item Type: Thesis (MPhil)
Status: Unpublished
Schools: Biosciences
Subjects: Q Science > QR Microbiology
Date of First Compliant Deposit: 30 March 2016
Last Modified: 24 Oct 2017 13:04
URI: https://orca.cardiff.ac.uk/id/eprint/43538

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