help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bruce-Keller, A. J.
Right arrow Articles by Mattson, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bruce-Keller, A. J.
Right arrow Articles by Mattson, M. P.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ESTRADIOL
Endocrinology Vol. 141, No. 10 3646-3656
Copyright © 2000 by The Endocrine Society

ARTICLES

Antiinflammatory Effects of Estrogen on Microglial Activation1

Annadora J. Bruce-Keller, Jonathan L. Keeling, Jeffrey N. Keller, Feng F. Huang, Simonetta Camondola and Mark P. Mattson

Department of Anatomy and Neurobiology (A.J.B.-K., J.L.K.) and Sanders-Brown Center on Aging (J.N.K., F.F.H.), University of Kentucky, Lexington, Kentucky 40536; and Laboratory of Neurosciences, National Institute on Aging (S.C., M.P.M.), Baltimore, Maryland 21224

Address all correspondence and requests for reprints to: Dr. Annadora J. Bruce-Keller, Mn 210 Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298. E-mail: abruce{at}pop.uky.edu

In the present study the effects of 17ß-estradiol on microglial activation are described. Estrogen replacement therapy has been associated with decreased severity of age-related neurodegenerative diseases such as Alzheimer’s disease, and estrogens have potent immunosuppressive properties outside of the brain. To determine the role that microglial cells might play in estrogen-mediated neuroprotection, primary rat microglia and N9 microglial cell lines were treated with increasing doses of 17ß-estradiol before or during immunostimulation by lipopolysaccharide, phorbol ester, or interferon-{gamma}. Pretreatment with 17ß-estradiol, but not 17{alpha}-estradiol or progesterone, dose dependently attenuated microglial superoxide release and phagocytic activity. Additionally, 17ß-estradiol attenuated increases in inducible nitric oxide synthase protein expression, but did not alter nuclear factor-{kappa}B activation. The antiinflammatory effects of 17ß-estradiol were blocked by the antiestrogen ICI 182,780. Additionally, 17ß-estradiol induced rapid phosphorylation of the p42/p44 mitogen-activated protein kinase (MAP kinase), and the MAP kinase inhibitor PD 98059 blocked the antiinflammatory effects of 17ß-estradiol. Overall, these results suggest that estrogen receptor-dependent activation of MAP kinase is involved in estrogen-mediated antiinflammatory pathways in microglial cells. These results describe a novel mechanism by which estrogen may attenuate the progression of neurodegenerative disease and suggest new pathways for therapeutic intervention in clinical settings.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
S. Tapia-Gonzalez, P. Carrero, O. Pernia, L. M Garcia-Segura, and Y. Diz-Chaves
Selective oestrogen receptor (ER) modulators reduce microglia reactivity in vivo after peripheral inflammation: potential role of microglial ERs
J. Endocrinol., July 1, 2008; 198(1): 219 - 230.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
K. Vagnerova, I. P. Koerner, and P. D. Hurn
Gender and the Injured Brain
Anesth. Analg., July 1, 2008; 107(1): 201 - 214.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
K. Hayakawa, K. Mishima, M. Nozako, M. Hazekawa, S. Mishima, M. Fujioka, K. Orito, N. Egashira, K. Iwasaki, and M. Fujiwara
Delayed Treatment With Minocycline Ameliorates Neurologic Impairment Through Activated Microglia Expressing a High-Mobility Group Box1-Inhibiting Mechanism
Stroke, March 1, 2008; 39(3): 951 - 958.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
R. H. Straub
The Complex Role of Estrogens in Inflammation
Endocr. Rev., August 1, 2007; 28(5): 521 - 574.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. M. Curran, B. M. Judy, N. A. Duru, H.-Q. Wang, L. A. Vergara, D. B. Lubahn, and D. M. Estes
Estrogenic Regulation of Host Immunity against an Estrogen Receptor-Negative Human Breast Cancer
Clin. Cancer Res., October 1, 2006; 12(19): 5641 - 5647.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. Canesi, C. Ciacci, L. C. Lorusso, M. Betti, T. Guarnieri, S. Tavolari, and G. Gallo
Immunomodulation by 17beta-estradiol in bivalve hemocytes
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R664 - R673.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
C. D. Bushnell, P. Hurn, C. Colton, V. M. Miller, G. del Zoppo, M. S.V. Elkind, B. Stern, D. Herrington, G. Ford-Lynch, P. Gorelick, et al.
Advancing the Study of Stroke in Women: Summary and Recommendations for Future Research From an NINDS-Sponsored Multidisciplinary Working Group
Stroke, September 1, 2006; 37(9): 2387 - 2399.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. Vegeto, S. Belcredito, S. Ghisletti, C. Meda, S. Etteri, and A. Maggi
The Endogenous Estrogen Status Regulates Microglia Reactivity in Animal Models of Neuroinflammation
Endocrinology, May 1, 2006; 147(5): 2263 - 2272.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
G. D. Barish, M. Downes, W. A. Alaynick, R. T. Yu, C. B. Ocampo, A. L. Bookout, D. J. Mangelsdorf, and R. M. Evans
A Nuclear Receptor Atlas: Macrophage Activation
Mol. Endocrinol., October 1, 2005; 19(10): 2466 - 2477.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
L. W. Baum
Sex, Hormones, and Alzheimer's Disease
J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(6): 736 - 743.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. Soucy, G. Boivin, F. Labrie, and S. Rivest
Estradiol Is Required for a Proper Immune Response to Bacterial and Viral Pathogens in the Female Brain
J. Immunol., May 15, 2005; 174(10): 6391 - 6398.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
R. G. Smith, L. Betancourt, and Y. Sun
Molecular Endocrinology and Physiology of the Aging Central Nervous System
Endocr. Rev., April 1, 2005; 26(2): 203 - 250.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Adamski and E. N. Benveniste
17{beta}-Estradiol Activation of the c-Jun N-Terminal Kinase Pathway Leads to Down-Regulation of Class II Major Histocompatibility Complex Expression
Mol. Endocrinol., January 1, 2005; 19(1): 113 - 124.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. J. Polanczyk, R. E. Jones, S. Subramanian, M. Afentoulis, C. Rich, M. Zakroczymski, P. Cooke, A. A. Vandenbark, and H. Offner
T Lymphocytes Do Not Directly Mediate the Protective Effect of Estrogen on Experimental Autoimmune Encephalomyelitis
Am. J. Pathol., December 1, 2004; 165(6): 2069 - 2077.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. E. Baker, V. M. Brautigam, and J. J. Watters
Estrogen Modulates Microglial Inflammatory Mediator Production via Interactions with Estrogen Receptor {beta}
Endocrinology, November 1, 2004; 145(11): 5021 - 5032.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Adamski, Z. Ma, S. Nozell, and E. N. Benveniste
17{beta}-Estradiol Inhibits Class II Major Histocompatibility Complex (MHC) Expression: Influence on Histone Modifications and CBP Recruitment to the Class II MHC Promoter
Mol. Endocrinol., August 1, 2004; 18(8): 1963 - 1974.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
Y. W. Lee, S. Y. Eum, A. Nath, and M. Toborek
Estrogen-mediated protection against HIV Tat protein-induced inflammatory pathways in human vascular endothelial cells
Cardiovasc Res, July 1, 2004; 63(1): 139 - 148.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
L. Zhao and R. D. Brinton
Suppression of Proinflammatory Cytokines Interleukin-1{beta} and Tumor Necrosis Factor-{alpha} in Astrocytes by a V1 Vasopressin Receptor Agonist: A cAMP Response Element-Binding Protein-Dependent Mechanism
J. Neurosci., March 3, 2004; 24(9): 2226 - 2235.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. M. Garcia-Segura and M. M. McCarthy
Minireview: Role of Glia in Neuroendocrine Function
Endocrinology, March 1, 2004; 145(3): 1082 - 1086.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Tzagarakis-Foster, R. Geleziunas, A. Lomri, J. An, and D. C. Leitman
Estradiol Represses Human T-cell Leukemia Virus Type 1 Tax Activation of Tumor Necrosis Factor-alpha Gene Transcription
J. Biol. Chem., November 15, 2002; 277(47): 44772 - 44777.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
I. Kadish and T. van Groen
Low Levels of Estrogen Significantly Diminish Axonal Sprouting after Entorhinal Cortex Lesions in the Mouse
J. Neurosci., May 15, 2002; 22(10): 4095 - 4102.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Guo, J. Krucken, W. P. M. Benten, and F. Wunderlich
Estradiol-induced Nongenomic Calcium Signaling Regulates Genotropic Signaling in Macrophages
J. Biol. Chem., February 22, 2002; 277(9): 7044 - 7050.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz
Changes in Proinflammatory Cytokine Activity after Menopause
Endocr. Rev., February 1, 2002; 23(1): 90 - 119.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Matsuda, M. T. Vanier, Y. Saito, K. Suzuki, and K. Suzuki
Dramatic phenotypic improvement during pregnancy in a genetic leukodystrophy: estrogen appears to be a critical factor
Hum. Mol. Genet., November 1, 2001; 10(23): 2709 - 2715.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Takeda, T. Ichiki, T. Tokunou, N. Iino, and A. Takeshita
15-Deoxy-Delta 12,14-prostaglandin J2 and Thiazolidinediones Activate the MEK/ERK Pathway through Phosphatidylinositol 3-Kinase in Vascular Smooth Muscle Cells
J. Biol. Chem., December 21, 2001; 276(52): 48950 - 48955.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2000 by The Endocrine Society