Journal Article

17β-Estradiol suppresses <i>Helicobacter pylori</i>-induced gastric pathology in male hypergastrinemic INS-GAS mice

Masahiro Ohtani, Zhongming Ge, Alexis García, Arlin B. Rogers, Sureshkumar Muthupalani, Nancy S. Taylor, Shilu Xu, Koichiro Watanabe, Yan Feng, Robert P. Marini, Mark T. Whary, Timothy C. Wang and James G. Fox

in Carcinogenesis

Volume 32, issue 8, pages 1244-1250
Published in print August 2011 | ISSN: 0143-3334
Published online May 2011 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgr072
17β-Estradiol suppresses Helicobacter pylori-induced gastric pathology in male hypergastrinemic INS-GAS mice

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Helicobacter pylori-associated gastric cancer is male predominant and animal studies suggest that sex hormones influence gastric carcinogenesis. We investigated the effects of 17β-estradiol (E2) or castration on H.pylori-induced gastritis in male INS-GAS/FVB/N (Tg(Ins1-GAS)1Sbr) mice. Comparisons were made to previously evaluated sham (n = 8) and H.pylori-infected (n = 8), intact male INS-GAS mice which had developed severe corpus gastritis accompanied by atrophy, hyperplasia, intestinal metaplasia and dysplasia of the epithelium within 16 weeks postinfection (all P < 0.01). Castration at 8 weeks of age had no sparing effect on lesions in uninfected (n = 5) or H.pylori-infected mice (n = 7) but all lesion subfeatures were attenuated by E2 in H.pylori-infected mice (n = 7) (P < 0.001). Notably, inflammation was not reduced but glandular atrophy, hyperplasia, intestinal metaplasia and dysplasia were also less severe in uninfected, E2-treated mice (n = 7) (P < 0.01). Attenuation of gastric lesions by E2 was associated with lower messenger RNA (mRNA) expression of interferon (IFN)-γ (P < 0.05) and interleukin (IL)-1β (P < 0.004), and higher IL-10 (P < 0.02) as well as decreased numbers of Foxp3+ regulatory T cells when compared with infected intact males. Infected E2-treated mice also developed higher Th2-associated anti-H.pylori IgG1 responses (P < 0.05) and significantly lower Ki-67 indices of epithelial proliferation (P < 0.05). E2 elevated expression of mRNA for Foxp3 (P < 0.0001) and IL-10 (P < 0.01), and decreased IL-1β (P < 0.01) in uninfected, intact male mice compared with controls. Therefore, estrogen supplementation, but not castration, attenuated gastric lesions in H.pylori-infected male INS-GAS mice and to a lesser extent in uninfected mice, potentially by enhancing IL-10 function, which in turn decreased IFN-γ and IL-1β responses induced by H.pylori.

Journal Article.  5002 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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