(taken from the application) Helicobacter pylori is responsible for chronic inflammation in the gastric mucosa. We propose that a long-term carrier state is the result of a balance of pro-inflammatory mediators and regulatory elements that maintain mucosal integrity. Mucosal damage results from a disruption of this balance, leading to sequelae such as ulceration, MALT, and adenocarcinoma.
Our aim i s to investigate the role of NO, prostaglandin E2, and cytokines in mediating both mucosal protection and damage during Helicobacter infections. We have preliminary data indicating that H. pylori interacts with gastric epithelial cells to induce both interleukin-8 and nitric oxide synthesis. In addition, NO has an effect on growth and morphology of H. pylori. The IL-8 induction in gastric epithelial cells is dependent on the expression of the cag pathogenicity in H. pylori, which encodes numerous proteins potentially involved in the secretion of virulence factors. Therefore, we will study isogenic mutants in this pathogenicity island with respect to their ability to induce inflammatory mediators in gastric epithelial cells. We have established a mouse model of infection with H. pylori, and propose to study iNOS induction, cox-2 induction, and cytokine profiles in infected mice. In addition, gastric epithelial cell lines will be used to optimize conditions and give preliminary data. Finally, iNOS, IL-4, IL-10 and IFN-g knockout mice will also be used to determine the importance of these enzymes and cytokines in H. pylon-induced gastritis.
| Cole, Sheri P; Harwood, Julia; Lee, Richard et al. (2004) Characterization of monospecies biofilm formation by Helicobacter pylori. J Bacteriol 186:3124-32 |
| Obonyo, Marygorret; Guiney, Donald G; Fierer, Joshua et al. (2003) Interactions between inducible nitric oxide and other inflammatory mediators during Helicobacter pylori infection. Helicobacter 8:495-502 |
| Hase, Koji; Murakami, Masamoto; Iimura, Mitsutoshi et al. (2003) Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology 125:1613-25 |
| Guiney, Donald G; Hasegawa, Patty; Cole, Sheri P (2003) Helicobacter pylori preferentially induces interleukin 12 (IL-12) rather than IL-6 or IL-10 in human dendritic cells. Infect Immun 71:4163-6 |
| Obonyo, Marygorret; Guiney, Donald G; Harwood, Julia et al. (2002) Role of gamma interferon in Helicobacter pylori induction of inflammatory mediators during murine infection. Infect Immun 70:3295-9 |
