Abstract
The influence of Helicobacter pylori infection on gastric epithelial cell proliferation, apoptosis and signaling pathways contributes to the development of infection-associated diseases. Here we report that JHP0290, which is a poorly functionally characterized protein from H. pylori, regulates multiple responses in human gastric epithelial cells. The differential expression and release of JHP0290 homologues was observed among H. pylori strains. JHP0290 existed in monomeric and dimeric forms in H. pylori cell extracts and culture broth. Recombinant purified JHP0290 (rJHP0290) also showed monomeric and dimeric forms, whereas the rJHP0290 C162A mutant exhibited only a monomeric form. The dimeric form of the protein was found to bind more efficiently to gastric epithelial cells than the monomeric form. The exposure of gastric epithelial cells to rJHP0290 induced proliferation in a dose-dependent manner. Faster progression into the cell cycle was observed in rJHP0290-challenged gastric epithelial cells. Furthermore, we detected an anti-apoptotic effect of rJHP0290 in gastric epithelial cells when the cells were treated with rJHP0290 in combination with Camptothecin (CPT), which is an inducer of apoptosis. CPT-induced caspase 3 activation was significantly reduced in the presence of rJHP0290. In addition, the activation of ERK MAPK and the transcription factor NFκB was observed in rJHP0290-challenged gastric epithelial cells lines. Our results suggest that JHP0290 may affect H. pylori-induced gastric diseases via the regulation of gastric epithelial cell proliferation and anti-apoptotic pathways.
Highlights
Helicobacter pylori is a helix-shaped, Gram-negative bacterial pathogen that colonizes the gastric mucosa of more than half of the human population worldwide [1]
The same lysates were immunoblotted with antibodies against Urease and alkyl hydroperoxide reductase (AhpC), which are abundantly expressed in H. pylori
We reported that the JHP0290 protein of H. pylori strain J99 is released into the culture broth by the bacterium [42]
Summary
Helicobacter pylori is a helix-shaped, Gram-negative bacterial pathogen that colonizes the gastric mucosa of more than half of the human population worldwide [1]. Infection with this bacterium is primarily asymptomatic, persistence may lead to severe gastroduodenal pathologies, such as chronic gastritis, peptic ulcers, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma [2]. The co-expression of CagA and H. pylori heat shock protein B (HspB) was found to induce gastric epithelial cell proliferation independent of bacterial infection [29]. H. pylori lipopolysaccharide (LPS) and the SlyD protein have been demonstrated to induce proliferation and anti-apoptotic signaling pathways in gastric epithelial cell lines [15, 23]. The co-expression of CagA and HspB induces a faster progression into the cell cycle in gastric epithelial cells [29]
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