| Summary: | <i>Helicobacter pylori</i> infection is an important risk factor for developing gastric cancer. However, only a few <i>H. pylori</i>-infected people develop gastric cancer. Thus, other risk factors aside from <i>H. pylori</i> infection may be involved in gastric cancer development. This study aimed to investigate whether the nitrate-reducing bacteria isolated from patients with atrophic gastritis caused by <i>H. pylori</i> infection are risk factors for developing atrophic gastritis and gastric neoplasia. Nitrate-reducing bacteria were isolated from patients with atrophic gastritis caused by <i>H. pylori</i> infection. Among the isolated bacteria, <i>Actinomyces oris</i>, <i>Actinomyces odontolyticus</i>, <i>Rothia dentocariosa</i>, and <i>Rothia mucilaginosa</i> were used in the subsequent experiments. Cytokine inducibility was evaluated in monocytic cells, and mitogen-activated protein kinase (MAPK) activity and cell cycle were assessed in the gastric epithelial cells. The cytotoxicities and neutrophil-inducing abilities of the <i>Actinomyces</i> and <i>Rothia</i> species were enhanced when cocultured with <i>H. pylori</i>. Th1/Th2-related cytokines were also expressed, but their expression levels differed depending on the bacterial species. Moreover, <i>H. pylori</i> and <i>Actinomyces</i> activated MAPK (ERK and p38) and affected cell cycle progression. Some nitrate-reducing bacteria cocultured with <i>H. pylori</i> may promote inflammation and atrophy by inducing cytokine production. In addition, the MAPK activation and cell cycle progression caused by these bacteria can contribute to gastric cancer development.
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