Modulatory effects of estrogen in two murine models of experimental colitis.
The association between oral contraceptives or pregnancy and inflammatory bowel disease is unclear. We investigated whether 17beta-estradiol modulates intestinal inflammation in two models of colitis. Female mice were treated with 17beta-estradiol alone or with tamoxifen, tamoxifen alone, 17 alpha-estradiol, or placebo. Dinitrobenzene sulfonic acid (DNB)- or dextran sodium sulfate (DSS)-induced colitis were assessed macroscopically, histologically, and by myeloperoxidase (MPO) activity. Malondialdehyde and mRNA levels of intercellular adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-gamma), and interleukin-13 (IL-13) were determined. In DNB colitis, 17beta-estradiol alone, but not 17beta-estradiol plus tamoxifen, or 17 alpha-estradiol reduced macroscopic and histological scores, MPO activity and malondialdehyde levels. 17beta-Estradiol also decreased the expression of ICAM-1, IFN-gamma, and IL-13 mRNA levels compared with placebo. In contrast, 17beta-Estradiol increased the macroscopic and histological scores compared with placebo in mice with DSS colitis. These results demonstrate anti-inflammatory and proinflammatory effects of 17beta-estradiol in two different models of experimental colitis. The net modulatory effect most likely reflects a combination of estrogen receptor-mediated effects and antioxidant activity and may explain, in part, conflicting results from clinical trials.
Verdú
Elena F
EF
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Deng
Yikang
Y
Bercik
Premysl
P
Collins
Stephen M
SM
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001557:Benzenesulfonates; D018793:Interleukin-13; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013629:Tamoxifen; C007488:dinitrobenzenesulfonic acid; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016264:Dextran Sulfate; D009195:Peroxidase