Helicobacter Pylori
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2005; 11(13): 1946-1950
Published online Apr 7, 2005. doi: 10.3748/wjg.v11.i13.1946
Macrophage migration inhibitory factor stimulated by Helicobacter pylori increases proliferation of gastric epithelial cells
Harry Hua-Xiang Xia, Shiu Kum Lam, Annie O.O. Chan, Marie Chia Mi Lin, Hsiang Fu Kung, Keiji Ogura, Douglas E. Berg, Benjamin C. Y. Wong
Harry Hua-Xiang Xia, Shiu Kum Lam, Annie O.O. Chan, Benjamin C. Y. Wong, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
Marie Chia Mi Lin, Hsiang Fu Kung, Institute of Molecular Biology, The University of Hong Kong, Hong Kong, China
Keiji Ogura, Douglas E. Berg, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
Author contributions: All authors contributed equally to the work.
Supported by Two Competitive Earmarked Research Grant from the Research Grants Council of Hong Kong Special Administrative Region, China, No. HKU7318/01M and HKU7493/03M to Dr. HHX Xia
Correspondence to: Dr. Benjamin C. Y. Wong, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. bcywong@hku.hk
Telephone: +852-2855-4541 Fax: +852-2872-5828
Received: September 15, 2004
Revised: September 16, 2004
Accepted: November 29, 2004
Published online: April 7, 2005
Abstract

AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro.

METHODS: A cytotoxic wild-type H pylori strain (TN2)and its three isogenic mutants (TN2△cag, TN2△cagA and TN2△cagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter.

RESULTS: The wild-type strain and the isogenic mutants, TN2△cagA and TN2△cagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2△cag did not increase the release of MIF at any of the four ratios. 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2△cagA and TN2△cagE, but not from the mutant TN2△cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared.

CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H pylori-induced gastric epithelial cell proliferation.

Keywords: H pylori; MIF; PAI