Macrophages are a dynamic cell type and represent a key component of the immune response, with a broad range of activities throughout the body. They respond to external cues, including microbes, alarmins, and growth factors, to eliminate invading pathogens through initiation of inflammation. Subsequently, they carry out several regulatory roles, including clearance of cellular debris, the resolution of inflammation, and wound healing to restore tissue homeostasis after an inflammatory response. The ability of macrophages to change their phenotype in this manner must be tightly regulated, as dysregulated macrophage activity is central to the pathogenesis of both inflammatory and fibrotic autoimmune disorders, such as Rheumatoid Arthritis (RA) and Idiopathic Pulmonary Fibrosis (IPF), respectively. One of the mechanisms by which regulation of macrophages occurs is the microRNA network. MicroRNAs (miRNAs) are a class of short, non-protein coding RNAs that post-transcriptionally regulate gene expression through translational repression, destabilisation or degradation of target mRNA. miR-155 is a multi-functional miRNA that has roles in regulating the development and function of many immune cells, including macrophages. Abnormal expression of miR-155 is associated with a number of autoimmune disorders and cancers. We reported previously that miR-155 is elevated in RA and contributes to the chronic, pro- inflammatory response of macrophages by repressing key anti-inflammatory proteins. However, the role of miR-155 in the regulation of remodelling responses by macrophages is less well characterised. Modulation of miRNA activity in cells through the use of mimics and inhibitors has emerged as a potential therapeutic strategy for the treatment of diseases. Technologies involving the use of lipid vesicles as delivery agents for introducing therapeutics into target cells have shown potential in increasing the drug efficacy.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:744170 |
| Date | January 2018 |
| Creators | Morton, Brian Edward |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/9118/ |
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