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), its three isogenic mutants (TN2Deltacag, TN2DeltacagA and TN2DeltacagE) 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, TN2DeltacagA and TN2 DeltacagE, 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 TN2delta 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 TN2DeltacagA and TN2DeltacagE, but not from the mutant TN2Deltacag. 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.
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), its three isogenic mutants (TN2Deltacag, TN2DeltacagA and TN2DeltacagE) 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 humangastric 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, TN2DeltacagA and TN2 DeltacagE, 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 TN2delta 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 TN2DeltacagA and TN2DeltacagE, but not from the mutant TN2Deltacag. 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.
Authors: Y P de Jong; A C Abadia-Molina; A R Satoskar; K Clarke; S T Rietdijk; W A Faubion; E Mizoguchi; C N Metz; M Alsahli; T ten Hove; A C Keates; J B Lubetsky; R J Farrell; P Michetti; S J van Deventer; E Lolis; J R David; A K Bhan; C Terhorst; M A Sahli Journal: Nat Immunol Date: 2001-11 Impact factor: 25.606
Authors: R Kleemann; A Hausser; G Geiger; R Mischke; A Burger-Kentischer; O Flieger; F J Johannes; T Roger; T Calandra; A Kapurniotu; M Grell; D Finkelmeier; H Brunner; J Bernhagen Journal: Nature Date: 2000-11-09 Impact factor: 49.962
Authors: Jennifer M Noto; Kristie L Rose; Amanda J Hachey; Alberto G Delgado; Judith Romero-Gallo; Lydia E Wroblewski; Barbara G Schneider; Shailja C Shah; Timothy L Cover; Keith T Wilson; Dawn A Israel; Juan Carlos Roa; Kevin L Schey; Yana Zavros; M Blanca Piazuelo; Richard M Peek Journal: Mol Cell Proteomics Date: 2018-11-19 Impact factor: 5.911
Authors: S Kariya; M Okano; K Fukushima; S Nomiya; Y Kataoka; R Nomiya; H Akagi; K Nishizaki Journal: Clin Exp Immunol Date: 2008-08-22 Impact factor: 4.330
Authors: N J Shimwell; D G Ward; Y Mohri; T Mohri; L Pallan; M Teng; Y C Miki; M Kusunoki; O Tucker; W Wei; J Morse; P J Johnson Journal: Br J Cancer Date: 2012-09-11 Impact factor: 7.640