Beneficial effects of estrogen treatment in the HLA-B27 transgenic rat model of inflammatory bowel disease.

Content Provider	Semantic Scholar
Author	Albert, Leo M. Leathurby, Yelena Eckert, Amy M. Ciarletta, Agnes Kasaian, M. T.
Copyright Year	2004
Abstract	A well-established model of bowel inflammation is the HLA-B27 transgenic rat that exhibits a spontaneous disease phenotype resulting in chronic diarrhea caused by immune cell activation. Estrogens have previously been shown to modulate the immune system, and both estrogen receptors (ERalpha and ERbeta) are present in the intestine and cells of the immune system. Therefore, the ability of estrogen to ameliorate disease progression in the HLA-B27 transgenic rat was determined. HLA-B27 transgenic rats with chronic diarrhea were treated with 17alpha-ethynyl-17beta-estradiol (EE) for 5 days. EE treatment dramatically improved stool scores after only 3 days. Histological scores of the degree of ulceration, inflammatory cell infiltration, fibrosis, and lesion depth of the colon were also improved by EE treatment. Because neutrophil infiltration into the colon is involved in the development and propagation of disease, myeloperoxidase (MPO) activity was measured. MPO levels were reduced by 80% by EE treatment. Cotreatment with the pure ER antagonist ICI-182780 (ICI) blocked the effects of EE on stool character, MPO activity, and histology scores, strongly suggesting that the activity of EE is mediated through ER. Mast cell proteases can promote neutrophil infiltration, and gene expression analysis demonstrated that mast cell protease 1, 3, and 4 mRNA were all decreased in colons from estrogen-treated rats. In addition, a direct effect of estrogen on bone marrow-derived mast cell activity was demonstrated, suggesting that ER-mediated inactivation of mast cells may contribute to the improvement in the clinical sign and histological scores in this model.
Starting Page	29
Ending Page	36
Page Count	8
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://ajpgi.physiology.org/content/ajpgi/286/1/G118.full.pdf
PubMed reference number	12958017v1
Volume Number	286
Issue Number	1
Journal	American journal of physiology. Gastrointestinal and liver physiology
Language	English
Access Restriction	Open
Subject Keyword	Bone Marrow Chronic diarrhea Colon structure (body structure) Combined Modality Therapy Disease Phenotype Disease Progression Eighty Endopeptidases Estradiol Estrogen Receptor alpha Estrogen Receptor beta Estrogen Receptors Estrogens Exhibits as Topic Feces Fibrosis HLA Antigens HLA-B27 Bld Donr Ql Histocompatibility Antigens Class II ICI 182,780 Immune Cell Activation Process Inflammatory Bowel Diseases Intestinal Diseases Intestinal Wall Tissue Intestines Neutrophil Infiltration Peroxidase Ulcer mast cell
Content Type	Text
Resource Type	Article