Helicobacter bilis infection induces oxidative stress in and enhances the proliferation of human cholangiocytes.

Abstract

Helicobacter bilis, an enterohepatic Helicobacter species, represents a carcinogenic risk factor for cholangiocytes owing to the prevalence of infections in patients with biliary tract cancer, cholecystitis, and pancreaticobiliary maljunction. However, the effect of H.bilis infection on cholangiocytes and the process and mechanism of carcinogenesis are not known. We aimed to determine the effects of H.bilis on cholangiocytes, focusing on inflammation and oxidative stress. Helicobacter bilis and MMNK-1 cells were cocultured for 24 h and inflammatory cytokine secretion was evaluated. Furthermore, MMNK-1 cell proliferation, intracellular reactive oxidant species (ROS) production, and DNA damage caused by ROS were investigated. All factors were compared with and without H.bilis infection. Interleukin (IL)-6 and IL-8 secretion were significantly increased in MMNK-1 cocultures with H.bilis (IL-6, 24.3 ± 12.2 vs. 271.1 ± 286.4pg/ml; IL-8, 167.6 ± 78.7 vs. 1085.1 ± 1047.1 pg/ml, p < .05). MMNK-1 proliferation was also significantly higher in H.bilis cocultures (1.05 ± 0.02 vs. 1.00-fold, respectively; p < .05). Coculturing enhanced the production of ROS in MMNK-1 cells depending on the cell concentration of H.bilis (1.0 vs. 1.17 ± 0.06, p < .05); however, DNA injury was not observed in cocultures with H.bilis (5.35 ± 0.87 vs. 6.08 ± 0.55 pg/μl, p=.06). Helicobacter bilis infection induced ROS production in and enhanced the proliferation of cholangiocytes.