Helicobacter pyloriouter inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitro

Abstract

Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

“…Damage induced by OipA presence is usually correlated with a greater risk of GC onset or peptic as well as duodenal ulcer disease and depends on the duration of infection and a dose of H. pylori [222,223]. The synthesis of CagA and VacA is believed to be regulated by OipA expression [224]. OipA is more prevalently detected in the gastric biopsy specimens obtained from patients with gastric precancerous lesions than those with gastritis alone.…”

Virulence of Helicobacter pylori outer membrane proteins: an updated review

“…Several studies have reported that OipA can increase the secretion of interleukin-8 (IL-8) and other inflammatory factors to cause neutrophil infiltration, aggravating the inflammation in the stomach and helping H. pylori to colonize, and this is why it is called an outer inflammatory protein [42,44]. OipA also inhibits the apoptosis of gastric cells [45], reducing the incidence of β-catenin nuclear translocation and cancer when the oip gene is switched off [46]. However, an in vitro study showed that OipA did not induce an increase in IL-8 expression [42].…”

Penicillin‑binding protein 1A mutation‑positive Helicobacter�pylori promotes epithelial‑mesenchymal transition in gastric cancer via the suppression of microRNA‑134

“…SGC-7901 cells were microscopically enumerated using an improved Neubauer counting chamber. Monolayer SGC-7901 cells in a 6-well plate (10 5 /well) were incubated with H. pylori at a multiplicity of infection of 50:1 for 12 h at 37°C and 10% CO 2 , as previously described (25).…”