title: Effects of cyclooxygenase-1 and -2 gene disruption on Helicobacter pylori-induced gastric inflammation.
abstract: BACKGROUND
  Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation.
  
  
  METHODS
  Wild-type (WT), COX-1 and COX-2 heterozygous (COX-1+/- and COX-2+/-), and homozygous COX-deficient (COX-1-/- and COX-2-/-) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX-deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined.
  
  
  RESULTS
  COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX-deficient mice, whereas cell proliferation was increased in WT and COX-1-deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-alpha and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-alpha mRNA expression was further increased by COX deficiency. Prostaglandin E2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B4 and LTC4 levels were increased to a similar extent in infected WT and COX-deficient mice.
  
  
  CONCLUSIONS
  COX deficiency enhances H. pylori-induced gastritis, probably via TNF-alpha expression. COX-2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation.
authors.affiliation: Department of Medicine, Queen Mary Hospital, Hong Kong, People's Republic of China.
authors.forename: Guo Qing
authors.initials: GQ
authors.lastname: Li
authors.forename: Harry Hua-Xiang
authors.initials: HH
authors.lastname: Xia
authors.forename: Min Hu
authors.initials: MH
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.forename: Ji De
authors.initials: JD
authors.lastname: Wang
authors.forename: Jun Zhong
authors.initials: JZ
authors.lastname: Peng
authors.forename: Annie O O
authors.initials: AO
authors.lastname: Chan
authors.forename: Chi Hin
authors.initials: CH
authors.lastname: Cho
authors.forename: Hau Leung
authors.initials: HL
authors.lastname: So
authors.forename: Shiu Kum
authors.initials: SK
authors.lastname: Lam
authors.forename: Pin Jin
authors.initials: PJ
authors.lastname: Hu
authors.forename: Ying Jie
authors.initials: YJ
authors.lastname: Liang
authors.forename: Han Liang
authors.initials: HL
authors.lastname: Lin
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
authors.forename: Zhe Hui
authors.initials: ZH
authors.lastname: Feng
authors.forename: Robert
authors.initials: R
authors.lastname: Langenbach
authors.forename: Benjamin Chun-Yu
authors.initials: BC
authors.lastname: Wong
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D051545:Cyclooxygenase 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D016753:Interleukin-10 / Q000235:genetics; D007975:Leukotriene B4 / Q000032:analysis; D017997:Leukotriene C4 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007975:Leukotriene B4; D017997:Leukotriene C4; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone