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Am J Physiol Gastrointest Liver Physiol (February 20, 2002). doi:10.1152/ajpgi.00460.2001
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Articles in PresS, published online ahead of print February 20, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00460.2001
Submitted on October 31, 2001
Accepted on February 4, 2002

The Modulatory Effects of Estrogen in Two Murine Models of Experimental Colitis

Elena F Verdu, Yikang Deng, Premysl Bercik, and Stephen M Collins*

* To whom correspondence should be addressed. E-mail: bercikp{at}mcmaster.ca.

The association between oral contraceptives, or pregnancy and inflammatory bowel disease is unclear. We investigated whether 17ß-estradiol modulates intestinal inflammation in two models of colitis. Female mice were treated with 17ß-estradiol alone or with tamoxifen, 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 adhesion molecule ICAM-1, interferon-{gamma} (IFN{gamma}) and IL-13 were determined. In DNB colitis, 17ß−estradiol, but not 17ß-estradiol plus tamoxifen or 17{alpha}-estradiol, reduced macroscopic and histologic scores, MPO activity and malondialdehyde levels. 17ß-Estradiol also decreased the expression of ICAM-1, IFN{gamma} and IL-13 mRNA levels compared to placebo. In contrast, 17ß-estradiol increased the macroscopic and histologic scores compared to placebo in mice with DSS colitis. These results demonstrate anti-inflammatory and pro-inflammatory effects of 17ß-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.




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