The TNF-Alpha Inducing Protein is Associated With Gastric Inflammation and Hyperplasia in a Murine Model of Infection.

() is a Gram-negative bacterium that colonizes the human stomach leading to the development of chronic gastritis, peptic ulcers and gastric adenocarcinoma. A combination of host, environment and bacterial virulence factors contribute to disease development. The TNFα inducing protein (Tipɑ) is a virulence factor shown to induce multiple pro-inflammatory cytokines in addition to TNFα . The goal of the present study was to elucidate the role of Tipα in promoting inflammation and to identify the molecular pathways associated with Tipα associated virulence. Mice were infected with wild-type Sydney strain (SS1) or a mutant (Δ) for 1 month and 4 months. We also completed a second 4 months infection including a 1:1 SS1 to Δ co-infected group in addition to SS1 and Δ infected groups. The expression of TNFα, and KC were significantly higher in the SS1 infected group compared to both uninfected control (naïve) and Δ groups. Mice infected with Tipα expressing SS1 induced more severe histological gastritis and developed hyperplasia compared to Δtipα infected mice. Microarray analysis of gastric epithelial cells co-cultured with recombinant Tipα (rTipα) demonstrates up-regulation of the NFκB pathway. This data suggest Tipα plays an important role in induced inflammation.