title: [Effects of Helicobacter pylori and Helicobacter pylori-related cytokines on apoptosis of gastric epithelial cells and mechanisms thereof].
abstract: OBJECTIVE
  To investigate the influence of Helicobacter pylori (H. pylori) and H. pylori-related cytokines on the apoptosis of gastric epithelial cells and mechanisms thereof.
  
  
  METHODS
  (1) Human gastric cancer cells of the line AGS and human gastric epithelial cells of the line GES-1 were cultured as control group, or incubated with H. pylori alone or H. pylori in combination with exogenous cytokines: interleukin (IL)-1beta, IL-8, or IL-10 for 24 hours. Then flow cytometry (FCM) was used to determine the rate of apoptosis. (2) The GES-1 and AGS cells were incubated with H. pylori for 24 hours and exogenous cytokines for 2 hours respectively. Then RT-PCR was used to examine the level of Fas mRNA expression. (3) Another GES-1 and AGS cells were cultured as control group, or incubated with FasL alone or FasL + exogenous cytokine for 2 hours (incubated with IL-1beta, IL-8, or IL-10 for 2 hours before being added with FasL). Then FCM was used to detect the apoptosis rate.
  
  
  RESULTS
  (1) In comparison to the apoptosis level of control group, H. pylori induced an increase in the apoptosis rate of GES-1 and AGS cells by 113.0% and 47.0% respectively (both P < 0.05). The H. pylori-induced apoptosis rates of GES-1 cells (by 29.6% or 25.8%) and AGS cells (by 19.7% or 21.1%) were reduced by IL-1beta or IL-10 (all P < 0.05). IL-8 increased the H. pylori-induced apoptosis level of GES-1 cells by 19.9% (P < 0.05). (2) In the baseline status, both GES-1 and AGS cells showed Fas mRNA expression. The Fas mRNA expressions of the GES-1 and AGS cells incubated with H. pylori were increased by 89.0% and 36.0% respectively (both P < 0.05) in comparison to that of the control group. IL-1beta and IL-10 had no significant effect on the basal Fas mRNA expressions in both GES-1 and AGS cells (all P > 0.05). IL-8 up-regulated the basal Fas mRNA expression level of the GES-1 cells by 33.0% (P < 0.05). (3) IL-1beta and IL-10 inhibited the FasL-induced apoptosis rate of the GES-1 cells (by 30.3% and 32.5% respectively) and AGS cells (by 44.2% and 51.5% respectively) (all P < 0.05). IL-8 enhanced the FasL-induced apoptosis level of the GES-1 cells by 100% (P < 0.05).
  
  
  CONCLUSIONS
  The gastric epithelium apoptosis induced by H. pylori may be in association with Fas receptor. IL-8 may enhance the H. pylori-induced apoptosis by up-regulating the Fas receptor expression. IL-1beta and IL-10 may modulate the apoptosis through other mechanisms.
authors.affiliation: Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Jia-ming
authors.initials: JM
authors.lastname: Qian
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Li
authors.forename: Yu-qing
authors.initials: YQ
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D053222:Fas Ligand Protein / Q000494:pharmacology; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000235:genetics
chemical_list: D016207:Cytokines; C491901:FAS protein, human; D053222:Fas Ligand Protein; D053583:Interleukin-1beta; D016209:Interleukin-8; D012333:RNA, Messenger; D019014:fas Receptor; D016753:Interleukin-10