Visit our Expo - Redox and Inflammation signaling 2012

VIII. Inflammation specific signaling Poster VIII, 18
Molecular mechanisms underlying inflammatory responses to Helicobacter pylori
infection
Jeong-Sang Lee1, Ki-Baik Hahm2, Jeffrey A. Johnson3, and Young-Joon Surh1
1National Research Laboratory of Molecular Carcinogenesis and Chemoprevention,
College of Pharmacy, Seoul National University. Seoul 151-742, 2Genomic Research
Center for Gastroenterology, School of Medicine, Ajou University, Suwon 442-749,
South Korea, and 3School of Pharmacy, University of Wisconsin, Madison, WI, USA
The Helicobacter pylori (H. pylori) were identified by Marshall and Warren in 1983. The H.
pylori survive in the forbidding harsh acid environment of the stomach and duodenum by
hiding in the mucus layer and neutralizing stomach acid in its local surrounding environment.
Multiple lines of evidences suggest that H. pylori infection is one of the primary causes of
gastritis and peptic ulcer, which are provoked by oxidative stress and inflammation. More
than 50% of the world's population is infected by this bacterium. The H. pylori–induced
inflammation has been implicated in the pathogenesis and progression of gastric cancer. In the
present study, we investigated molecular mechanisms responsible for H. pylori-induced
inflammation in human gastric cancer (AGS) cells. H. pylori induced inflammatory response
accompanied up-regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase
(iNOS), and both the secretion and protein expression of interleukin-8 (IL-8) in AGS cells.
The nuclear translocation and subsequent DNA binding of nuclear factor-kappaB (NF-!B), a
eukaryotic transcription factor known to regulate aforementioned pro-inflammatory enzymes
and mediators, were increased after H. pylori treatment. Similarly, the DNA binding of
eukaryotic transcription factor activator protein-1 (AP-1) was induced by H. pylori treatment.
In addition, c-Jun that is the major component of AP-1 was detected by super shift assay, and
the level of phospho-c-Jun was found to be increased. H. pylori infection accelerated the
DNA binding of another transcription factor CREB, whose interacting partners were detected
as CREB and CBP as determined by the super shift assay. In another experiment, H. pylori –
infected AGS cells exhibited increased phosphorylation of upstream kinases, ERK and AKT.
However, long term administration of H. pylori resulted in the activation of proliferating cell
nuclear antigens (PCNA) and Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End
Labeling (TUNEL) in C57BL6 mice, suggesting that H. pylori infection may create a balance
between proliferation and apoptotic process in the stomach. Taken together, H. pylori
treatment can cause the inflammatory response through up-regulation of proteins involved in
pro-inflammatory signal transduction.
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