[759] Upregulation of A20 Is Induced by Helicobacter pylori Infection in Gastric Epithelial Cells

Tomohisa Uchida, Lam T Nguyen, Masatsugu Moriyama. Oita University, Yufu, Oita, Japan; 108 Hospital, Hanoi, Viet Nam

Background: A20 is well known as a NF-κB suppressor and proapoptotic protein. NF-κB pathway activation caused by H. pylori infection induces inflammatory responses from host cells. However, the process by which gastric epithelial cells counteract H. pylori induced-NF-kB activation to avoid overreactions has not well analyzed yet. In this study, we investigated the role of A20 in H. pylori-gastric epithelium interaction.
Design: Gastric epithelial cell lines; AGS cell and MKN 45 cell were used. H. pylori were infected to gastric epithelial cells at MOI=100. A20 expression was analyzed by real-time RCR. NF-kB activation were quantified by luciferase assay. Il-8 concentration in supernatant were measured by ELISA.
Results: Upon H. pylori infection, A20 was upregulated in a time- and MOI-dependent manner. A20 mRNA increased sharply within 3 hours and then decreased gradually to the baseline after 36 hours. The induction of A20 by H. pylori depended on type IV secretion system as cagE and cagPAI mutants of H. pylori lost almost all the ability to induce A20. Nevertheless, cagA mutant strain is still able to trigger A20 upregulation but this ability was reduced considerably, indicating that A20 induction was partly cagA-dependent. Because H. pylori injects CagA protein and its peptidoglycan into the host cell via type IV secretion system. Transfection of cagA vector and H. pylori peptidoglycan resulted in a significant increase of A20 expression. We overexpressed A20 in gastric cells and infected them with H. pylori. We saw that the activation of NF-κB in these cells was suppressed significantly. Similarly, the knock-down of A20 by siRNA increase NF-κB activation dramatically.
Conclusions: These findings indicate that H. pylori induces A20 expression in host cell to restrain H. pylori-activated NF-kB. This negative feed-back loop will establish the balance between host and infectant.
Category: Gastrointestinal

Wednesday, March 6, 2013 1:00 PM

Poster Session VI # 72, Wednesday Afternoon


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