The goal of this project is to determine the range and mechanism of action of phytoestrogens (genistein, diadzein and soy extracts) on innate immune function via estrogen receptor-dependent and independent pathways. This goal will be accomplished using estrogen receptor deficient (ERKO) severe combined immunodeficient (SCID) mouse models of bacterial inflammation in the gut, liver and spleen. The hypothesis is that estrogen and phytoestrogen signaling is a positive regulator of macrophage and natural killer cell function. Specifically, this project will: 1) Determine the effects of the loss of estrogen receptor alpha signaling on bacterial-induced inflammation. 2) Determine the effects of the loss of estrogen receptor beta signaling on bacterial-induced inflammation. 3) Determine the effects of the loss of estrogen receptors alpha and beta signaling on bacterial induced inflammation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
1P01ES010535-01
Application #
6359974
Study Section
Special Emphasis Panel (ZRG1-BNP (02))
Project Start
2000-03-01
Project End
2005-02-28
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
$65,390
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
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Slusarz, Anna; Jackson, Glenn A; Day, J Kevin et al. (2012) Aggressive prostate cancer is prevented in ER?KO mice and stimulated in ER?KO TRAMP mice. Endocrinology 153:4160-70
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Wang, Qun; Tompkins, Kenneth D; Simonyi, Agnes et al. (2006) Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus. Brain Res 1090:182-9
Zhou, Wei; Liu, Zhilin; Wu, Jianbo et al. (2006) Identification and characterization of two novel splicing isoforms of human estrogen-related receptor beta. J Clin Endocrinol Metab 91:569-79
Wang, Qun; Yu, Sue; Simonyi, Agnes et al. (2005) Kainic acid-mediated excitotoxicity as a model for neurodegeneration. Mol Neurobiol 31:3-16
Lambert, K Chad; Curran, Edward M; Judy, Barbara M et al. (2005) Estrogen receptor alpha (ERalpha) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17beta-estradiol acts through ERalpha to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation. J Immunol 175:5716-23

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