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dc.contributor.advisorMcConnell, Michelle
dc.contributor.advisorKemp, Roslyn
dc.contributor.authorThomson, Kristian Leonard Jack
dc.date.available2014-09-10T03:58:17Z
dc.date.copyright2014
dc.identifier.citationThomson, K. L. J. (2014). The Immunological Role of Enterocytes and Probiotics in Necrotizing Enterocolitis (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/4970en
dc.identifier.urihttp://hdl.handle.net/10523/4970
dc.description.abstractNecrotizing enterocolitis (NEC) is an important and sometimes fatal intestinal disease that primarily affects premature neonates and although it has been extensively investigated, the complete pathogenesis of NEC remains unclear. Important immunological factors such as interleukin 8 (IL-8), toll like receptor 4 (TLR4), cluster of differentiation 14 (CD14), lipopolysaccharide (LPS), and also bacteria from the Enterobacteriaceae family have been implicated in the pathogenesis of NEC while probiotics have been used clinically as a prophylactic treatment. In order to produce more effective treatments, it is important to understand the pathophysiology of NEC and also the mechanism of action of probiotics. We demonstrate here that human colonic epithelial cells (HT-29 cells) are able to produce significantly increased amounts of IL-8 in response to purified bacterial LPS and 12 strains of Enterobacteriaceae, isolated from clinical NEC specimens, compared to unstimulated controls. This response was time and dose-dependent, and was confirmed by the use of another colonic epithelial cell line (Caco-2 cells). Two strains of clinically utilised probiotic bacteria (Bifidobacterium infantis and Lactobacillus acidophilus) did not induce IL-8 production by either intestinal epithelial cell (IEC). The addition of live B. infantis or a Gram positive cell wall component, lipoteichoic acid (LTA), was able to significantly reduce the IL-8 response seen during an LPS stimulation of HT-29 cells. No reduction in IL-8 production was demonstrated by heat inactivated probiotics or live L. acidophilus. CD14 and TLR4 were expressed by HT-29 cells and it was found that LPS induced IL-8 production was CD14-dependent. It has previously been shown that LPS and bacteria can induce an IL-8 response from intestinal epithelial cells and that probiotic bacteria are effective at reducing both this response and also the incidence of NEC. However, this is the first report of an immunological mechanism using these NEC-associated Enterobacteriaceae and probiotic strains and intestinal epithelial cells.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectNecrotizing enterocolitis
dc.subjectNEC
dc.subjectIL-8
dc.subjectCD14
dc.subjectTLR4
dc.subjectHT-29
dc.subjectvery low birth weight
dc.subjectpremature
dc.subjectneonate
dc.subjectprobiotics
dc.subjectEnterobacteriaceae
dc.subjectcolonisation
dc.subjectintestinal epithelial cells
dc.subjectenterocytes
dc.subjectbacteria
dc.subjectimmunology
dc.subjectmicrobiology
dc.subjectLPS
dc.subjectlipopolysaccharide
dc.subjectendotoxin
dc.subjectpro-inflammatory
dc.subjectmucosal barrier
dc.subjectLactobacillus acidophilus
dc.subjectBifidobacterium infantis
dc.titleThe Immunological Role of Enterocytes and Probiotics in Necrotizing Enterocolitis
dc.typeThesis
dc.date.updated2014-09-10T03:32:52Z
dc.language.rfc3066en
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.openaccessOpen
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