Helicobacter pylori
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2005; 11(40): 6305-6311
Published online Oct 28, 2005. doi: 10.3748/wjg.v11.i40.6305
Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization
Tomokazu Mizuno, Takafumi Ando, Kazuo Nobata, Tomoyuki Tsuzuki, Osamu Maeda, Osamu Watanabe, Masaaki Minami, Kenji Ina, Kazuo Kusugami, Richard M. Peek, Hidemi Goto
Tomokazu Mizuno, Takafumi Ando, Masaaki Minami, Osamu Watanabe, Kazuo Nobata, Tomoyuki Tsuzuki, Osamu Maeda, Kenji Ina, Kazuo Kusugami, Hidemi Goto, Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Richard M. Peek, Division of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Takafumi Ando, Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. takafumia-gi@umin.ac.jp
Telephone: +81-52-7442144 Fax: +81-52-7442175
Received: December 30, 2004
Revised: February 15, 2005
Accepted: February 18, 2005
Published online: October 28, 2005
Abstract

AIM: 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 μg/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.

CONCLUSION: 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.

Keywords: Helicobacter pylori, Gastric ulcer, Histological gastritis, Interleukin-17, Interleukin-8