Prostate carcinoma represents one of the leading causes of cancer death in men within the Western world, Several studies have hypothesised that chronic prostatic inflammation may predispose men to developing this malignancy. In 2005, the Gram-positive anaerobe, Propionibacterium acnes was identified as the predominant bacterium in cancerous prostate glands; with its pro-inflammatory nature illustrated following acute and chronic infection of such cells both in vitro and in vivo, The main objective of this study was therefore to further elucidate the potential role of p, acnes in the aetiology of prostate cancer. Firstly, the inflammatory response of normal prostate epithelial cells (RWPE-1s), following short-term exposure to a number of P. acnes phylogroups, was examined; with particular interest on the effects of infection on expression of pro-inflammatory molecules, such as PAR-2. Next, long-term infection studies Were performed to evaluate P. acnes persistence, and the mechanisms by which this bacterium stimulates chronic prostatic inflammation. Short-term P. acnes infection potently induced PAR-2 expression in RWPE-1s, as revealed by RT-PCR and Western! immunoblotling; with all strains also found to enhance secretion of inflammatory mediators, including IL-6 and IL-8. Distinct phylotypic differences were noted during these studies; thus underpinning reports of diversity among P. acnes phylotypes. Total viable counts demonstrated the ability of P. acnes to establish chronic RWPE-1 infection; thereby facilitating the induction of sustained prostatic inflammation, achieved through augmentation of PAR-2, and increased release of pro-inflammatory molecules, Moreover, qRT-PCR array analysis revealed P. acnes infection to upregulate many pro-angiogenic genes; a response reflected during in vitro tubule assays upon incubation of HMEC-1 s with conditioned media obtained from P. acnes-infected RWPE-1s. Taken together, the findings obtained these studies highlight prostatic P. acnes infection as a potential risk factor for prostate carcinogenesis, due to the strong inflammatory response that is generated upon exposure to such cells.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:678939 |
| Date | January 2015 |
| Creators | McCafferty, Darragh |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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