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The Role of the TNF-alpha Inducing Protein (Tipalpha) in the Host Immune and Inflammatory Response to Helicobacter pylori Infection
Başlık:
The Role of the TNF-alpha Inducing Protein (Tipalpha) in the Host Immune and Inflammatory Response to Helicobacter pylori Infection
Yazar:
Morningstar-Wright, Lindsay, author.
ISBN:
9780438028944
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (149 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Thomas G. Blanchard Committee members: Nicholas H. Carbonetti; Steven J. Czinn; Achsah D. Keegan; Joshua P. Lewis; Joao H.F. Pedra; David A. Rasko.
Özet:
Helicobacter pylori (H. pylori ) is a Gram-negative bacterium that colonizes the human stomach leading to the development of chronic gastritis, peptic ulcers and gastric cancer. It is estimated that 50% of the world population is infected with the bacterium and approximately 15--20% of those infected will develop gastric disease. It remains impossible to predict which individuals will develop disease, but it appears that host and environmental factors play a role along with bacterial virulence factors. A greater understanding of H. pylori virulence factors and their role in pathogenesis will help determine why over 80% of infected individuals remain unsymptomatic and healthy. The H. pylori Tumor necrosis factor- alpha (TNFalpha) inducing protein (Tipalpha) is a virulence factor shown to induce multiple pro-inflammatory cytokines in addition to TNFalpha, and is believed to contribute to cancer development. We hypothesize that Tipalpha will have a pro-infammatory effect on the host immune response and stimulate additional pro-inflammatory pathways in gastric epithelial cells that promote inflammation and carcinogenesis. Mouse infections with wild-type Sydney strain (SS1) and a Tipalpha mutant (Delta tipalpha) suggest that Tipalpha plays a significant role in promoting inflammation by the upregulation of several pro-inflammatory cytokines such as TNFalpha, Interferon-gamma (IFNgamma), Interleukin 17 (IL-17) and chemokine 1 (Cxcl1/KC) in mice and may play a role in the development of hyperplasia. A group of co-infected mice with a 1:1 mix of wild-type SS1: and Delta tipalpha had comparable cytokine expression and inflammation to the wild-type mice. Three out of ten animals were positive for Delta tipalpha in the co-infected group suggesting Deltatip alpha can be outcompeted during co-infection. Examination of N87 gastric epithelial cells co-cultured with Deltatipalpha showed similar gene expression and pathway analysis to N87 cells co-cultured with wild-type SS1 suggesting redundant mechanisms within the bacteria that induce similar responses to those induced by Tipalpha. The use of recombinant Tipalpha (rTipalpha) co-cultured with gastric epithelial cells shows the induction of pro-inflammatory upstream regulators TNFalpha, IFNgamma, IL-6 and IL-1. Overall, we identified some putitive gene targets of Tipalpha for further exploration in addition to previous pathways known to be affected by H. pylori infection.
Notlar:
School code: 0373
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(681349.1) | 681349-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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