title: Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization.
abstract: OBJECTIVE
  To determine the role of interleukin (IL)-17 in gastric ulcerogenesis.
  
  
  METHODS
  Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 microg/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori (H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26,695 or recombinant human (rh) IL-17.
  
  
  RESULTS
  All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2,499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P< 0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1,356 pg/mg/protein, range 121-1,3730; antrum: median 761 pg/mg/protein, range 24-7,620, P< 0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62, P< 0.0001; antrum: r = 0.61, P< 0.0001) in GU patients. RhIL-17 and H pylori strain 26,695 each stimulated IL-8 production from AGS cells.
  
  
  CONCLUSIONS
  IL-17 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Mizuno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nobata
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Osamu
authors.initials: O
authors.lastname: Maeda
authors.forename: Osamu
authors.initials: O
authors.lastname: Watanabe
authors.forename: Masaaki
authors.initials: M
authors.lastname: Minami
authors.forename: Kenji
authors.initials: K
authors.lastname: Ina
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kusugami
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013276:Stomach Ulcer / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D020381:Interleukin-17; D016209:Interleukin-8; D012333:RNA, Messenger; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori