title: Role of cagA-positive Helicobacter pylori on cell proliferation, apoptosis, and inflammation in biliary cells.
abstract: OBJECTIVE
  The pathogenesis of Helicobacter pylori in the human hepatobiliary system has not been clearly elucidated. We compared the effects of H. pylori cagA(+) and cagA(-) mutant strains on cell proliferation, apoptosis, and inflammation in a cholangiocarcinoma (CCA) cell line (KKU-100).
  
  
  METHODS
  MTT and BrdU were used to determine cell viability and DNA synthesis, respectively. The results were further investigated by RT-PCR and Western-blot analysis. The production of interleukin-8 (IL-8) was measured by ELISA assay.
  
  
  RESULTS
  At low H. pylori inocula (cell-bacteria ratio of 1:1), the H. pylori cagA(+) strain showed a significant stimulation in KKU-100 cell growth (109 ± 1.79%) and DNA synthesis (131 ± 3.39%) than did the H. pylori cagA(-) strain (95 ± 3.06% and 120 ± 2.32%, respectively), through activation of the anti-apoptotic bcl-2 gene, MAP kinase and NF- κB cascade. By contrast, at high H. pylori inocula (cell-bacteria ratio of 1:200), the H. pylori cagA(+) strain showed a significant reduction in KKU-100 cell survival (49 ± 2.47%) and DNA synthesis (49 ± 1.14%) than did the H. pylori cagA(-) strain (60 ± 1.30% and 75 ± 4.00%, respectively), by increased iNOS, p53 and bax, while decreased bcl-2. Additionally, caspase-8 and -3 protein were activated. The H. pylori cagA (+) strain had significantly stronger effect on IL-8 production than did the cagA(-) strain.
  
  
  CONCLUSIONS
  These results suggest that the H. pylori cagA(+) strain may play an important role in the development of biliary cancer by disturbing cell proliferation, apoptosis, and promoting cell inflammation in the CCA cell line.
authors.affiliation: Department of Microbiology, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. kong_55@hotmail.com
authors.forename: Wongwarut
authors.initials: W
authors.lastname: Boonyanugomol
authors.forename: Chariya
authors.initials: C
authors.lastname: Chomvarin
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Baik
authors.forename: Jea-Young
authors.initials: JY
authors.lastname: Song
authors.forename: Chariya
authors.initials: C
authors.lastname: Hahnvajanawong
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Myung-Je
authors.initials: MJ
authors.lastname: Cho
authors.forename: Woo-Kon
authors.initials: WK
authors.lastname: Lee
authors.forename: Hyung-Lyun
authors.initials: HL
authors.lastname: Kang
authors.forename: Kwang-Ho
authors.initials: KH
authors.lastname: Rhee
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001659:Biliary Tract / Q000166:cytology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000502:physiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori; D004247:DNA; D052247:Nitric Oxide Synthase Type II