The central hypothesis of this research is i) that gastric epithelial hyperplasia Helicobacter pylori infected mice is due to an imbalance, and ii) that this imbalance is mediated by pro-inflammatory cytokines (ie. IFN-gamma, IL-1 and TNF-alpha). This hypothesis is based upon four observations. First, both apoptosis and proliferation are increased in H. pylori-infected mice is dependent on an intact T-cell immune response. Finally, in-vitro data support the proposed relationship between apoptosis, hyperplasia and inflammatory cytokines. Preliminary data have shown that IFN-gamma increases apoptosis in cultured gastric epithelial cells, but conditioned media (which contain IFN-gamma) induce proliferation. Taken together, these data suggests that pre-neoplastic proliferation due to H. pylori is host-mediated, and that both proliferative and apoptotic mechanisms contribute. The initial aim of the study is to confirm the presence and relative quantity of IFN-gamma, IL-1, and TNF-alpha mRNA and protein in gastric tissue and conditioned media from gastric LPL of infected mice.
Aim 2 will evaluate the functional effect of these cytokines on gastric epithelial cell culture and will address the presence and up/down regulation of cytokine receptor mRNA and protein in the cells.
Aim 3 will address apoptosis in chronic H. pylori infection focusing on the Fas and TRAIL mechanisms. Compensatory hyperplasia secondary to the apoptosis will be evaluated.
The final aim will be to evaluate the role of gastric somal and epithelial cells in gastric proliferation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA090234-03
Application #
6633951
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Lohrey, Nancy
Project Start
2002-03-01
Project End
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2003
Total Cost
$49,864
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
071650709
City
Columbus
State
OH
Country
United States
Zip Code
43210