Abstract

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, the 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. The PI on this project is D. Mark Estes and the co-PI is Criag Franklin. Two consultants on the project are Helen Mullen and Dennis Lubahn. All of these personnel are based at the University of Missouri-Columbia. The sites for the research are the UM-C?s Horticulture and Agroforestery Research Center in New Franklin and the UM-C?s Southwest Research Station in Mt. Vernon.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
3P01ES010535-03S1
Application #
6647790
Study Section
Special Emphasis Panel (ZRG1)
Project Start
2002-03-01
Project End
2003-02-28
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
$65,390
Indirect Cost

  Institution

Name
University of Missouri-Columbia
Department
Type
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211

  Publications

Lei, Wei; Browning Jr, Jimmy D; Eichen, Peggy A et al. (2015) Immuno-stimulatory activity of a polysaccharide-enriched fraction of Sutherlandia frutescens occurs by the toll-like receptor-4 signaling pathway. J Ethnopharmacol 172:247-53
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
Brown, Marybeth; Ning, Jie; Ferreira, J Andries et al. (2009) Estrogen receptor-alpha and -beta and aromatase knockout effects on lower limb muscle mass and contractile function in female mice. Am J Physiol Endocrinol Metab 296:E854-61
Richter, Catherine A; Taylor, Julia A; Ruhlen, Rachel L et al. (2007) Estradiol and Bisphenol A stimulate androgen receptor and estrogen receptor gene expression in fetal mouse prostate mesenchyme cells. Environ Health Perspect 115:902-8
Zhou, Wei; Lo, Shih-Ching; Liu, Jing-Hua et al. (2007) ERRbeta: a potent inhibitor of Nrf2 transcriptional activity. Mol Cell Endocrinol 278:52-62
Curran, Edward M; Tassell, Audrey Hart-Van; Judy, Barbara M et al. (2007) Estrogen increases menopausal host susceptibility to experimental ascending urinary-tract infection. J Infect Dis 195:680-3
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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