Estrogen and brain inflammation: Effects on microglial expression of MHC, costimulatory molecules and cytokines

Filomena O. Dimayuga; Janelle L. Reed; Genevieve A. Carnero; Chunmei Wang; Edgardo R. Dimayuga; Vanessa M. Dimayuga; Andrea Perger; Melinda E. Wilson; Jeffrey N. Keller; Annadora J. Bruce-Keller

doi:10.1016/j.jneuroim.2004.12.016

Estrogen and brain inflammation: Effects on microglial expression of MHC, costimulatory molecules and cytokines

Filomena O. Dimayuga, Janelle L. Reed, Genevieve A. Carnero, Chunmei Wang, Edgardo R. Dimayuga, Vanessa M. Dimayuga, Andrea Perger, Melinda E. Wilson, Jeffrey N. Keller, Annadora J. Bruce-Keller

Research output: Contribution to journal › Article › peer-review

122 Scopus citations

Abstract

To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17β-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17β-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD152, CD28, CD8, CD11b, Fas, FasL, and also ERα and ERβ, were examined in N9 microglial cells. Additionally, the effects of 17β-estradiol on basal and LPS-induced release of cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-10) were determined. Data indicate that estrogen increases IL-10 while decreasing TNFα and IFNγ release from resting and LPS-stimulated N9 cells. Additionally, LPS-induced surface staining of MHC Class I, CD40, and CD86 was significantly attenuated by estrogen pretreatment. The basal percentage of cells positive for MHC Class I and II, CD40, and CD152, Fas, and FasL was significantly decreased by estrogen exposure. However, CD8, CD86, CD11b, and CD28 were unaffected by estrogen, and CD80 cell surface staining significantly increased following estrogen exposure. Taken together, these data indicate that estrogen can significantly decrease components of adaptive immunity in microglial cells, and highlight the multi-faceted regulatory effects of estrogen on microglial parameters related to antigen presentation and T cell interaction.

Original language	English
Pages (from-to)	123-136
Number of pages	14
Journal	Journal of Neuroimmunology
Volume	161
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2004.12.016
State	Published - Apr 2005

Bibliographical note

Funding Information:
The authors are grateful to Dr. P. Ricciardi-Castagnoli, of the Department of Biotechnology and Bioscience, Piazza della Scienza 2, University of Milano-Bicocca, Milan, Italy for the N9 cell lines. Additional gratitude goes to Ms. Jennifer Strange and Dr. Greg Bauman at the Flow Cytometry Facility of the University of Kentucky College of Medicine for FACS analysis and their thoughtful comments on the data. This work was supported by grants from the NIH (NS045601 and P20 RR15592).

Keywords

Antigen presentation
Cytokines
Microglial activation
Neuroinflammation
Sex steroids

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

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10.1016/j.jneuroim.2004.12.016

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@article{204443ccd2b24976a599b4259e3ed390,

title = "Estrogen and brain inflammation: Effects on microglial expression of MHC, costimulatory molecules and cytokines",

abstract = "To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17β-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17β-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD152, CD28, CD8, CD11b, Fas, FasL, and also ERα and ERβ, were examined in N9 microglial cells. Additionally, the effects of 17β-estradiol on basal and LPS-induced release of cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-10) were determined. Data indicate that estrogen increases IL-10 while decreasing TNFα and IFNγ release from resting and LPS-stimulated N9 cells. Additionally, LPS-induced surface staining of MHC Class I, CD40, and CD86 was significantly attenuated by estrogen pretreatment. The basal percentage of cells positive for MHC Class I and II, CD40, and CD152, Fas, and FasL was significantly decreased by estrogen exposure. However, CD8, CD86, CD11b, and CD28 were unaffected by estrogen, and CD80 cell surface staining significantly increased following estrogen exposure. Taken together, these data indicate that estrogen can significantly decrease components of adaptive immunity in microglial cells, and highlight the multi-faceted regulatory effects of estrogen on microglial parameters related to antigen presentation and T cell interaction.",

keywords = "Antigen presentation, Cytokines, Microglial activation, Neuroinflammation, Sex steroids",

author = "Dimayuga, {Filomena O.} and Reed, {Janelle L.} and Carnero, {Genevieve A.} and Chunmei Wang and Dimayuga, {Edgardo R.} and Dimayuga, {Vanessa M.} and Andrea Perger and Wilson, {Melinda E.} and Keller, {Jeffrey N.} and Bruce-Keller, {Annadora J.}",

note = "Funding Information: The authors are grateful to Dr. P. Ricciardi-Castagnoli, of the Department of Biotechnology and Bioscience, Piazza della Scienza 2, University of Milano-Bicocca, Milan, Italy for the N9 cell lines. Additional gratitude goes to Ms. Jennifer Strange and Dr. Greg Bauman at the Flow Cytometry Facility of the University of Kentucky College of Medicine for FACS analysis and their thoughtful comments on the data. This work was supported by grants from the NIH (NS045601 and P20 RR15592).",

year = "2005",

month = apr,

doi = "10.1016/j.jneuroim.2004.12.016",

language = "English",

volume = "161",

pages = "123--136",

number = "1-2",

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TY - JOUR

T1 - Estrogen and brain inflammation

T2 - Effects on microglial expression of MHC, costimulatory molecules and cytokines

AU - Dimayuga, Filomena O.

AU - Reed, Janelle L.

AU - Carnero, Genevieve A.

AU - Wang, Chunmei

AU - Dimayuga, Edgardo R.

AU - Dimayuga, Vanessa M.

AU - Perger, Andrea

AU - Wilson, Melinda E.

AU - Keller, Jeffrey N.

AU - Bruce-Keller, Annadora J.

N1 - Funding Information: The authors are grateful to Dr. P. Ricciardi-Castagnoli, of the Department of Biotechnology and Bioscience, Piazza della Scienza 2, University of Milano-Bicocca, Milan, Italy for the N9 cell lines. Additional gratitude goes to Ms. Jennifer Strange and Dr. Greg Bauman at the Flow Cytometry Facility of the University of Kentucky College of Medicine for FACS analysis and their thoughtful comments on the data. This work was supported by grants from the NIH (NS045601 and P20 RR15592).

PY - 2005/4

Y1 - 2005/4

N2 - To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17β-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17β-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD152, CD28, CD8, CD11b, Fas, FasL, and also ERα and ERβ, were examined in N9 microglial cells. Additionally, the effects of 17β-estradiol on basal and LPS-induced release of cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-10) were determined. Data indicate that estrogen increases IL-10 while decreasing TNFα and IFNγ release from resting and LPS-stimulated N9 cells. Additionally, LPS-induced surface staining of MHC Class I, CD40, and CD86 was significantly attenuated by estrogen pretreatment. The basal percentage of cells positive for MHC Class I and II, CD40, and CD152, Fas, and FasL was significantly decreased by estrogen exposure. However, CD8, CD86, CD11b, and CD28 were unaffected by estrogen, and CD80 cell surface staining significantly increased following estrogen exposure. Taken together, these data indicate that estrogen can significantly decrease components of adaptive immunity in microglial cells, and highlight the multi-faceted regulatory effects of estrogen on microglial parameters related to antigen presentation and T cell interaction.

AB - To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17β-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17β-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD152, CD28, CD8, CD11b, Fas, FasL, and also ERα and ERβ, were examined in N9 microglial cells. Additionally, the effects of 17β-estradiol on basal and LPS-induced release of cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-10) were determined. Data indicate that estrogen increases IL-10 while decreasing TNFα and IFNγ release from resting and LPS-stimulated N9 cells. Additionally, LPS-induced surface staining of MHC Class I, CD40, and CD86 was significantly attenuated by estrogen pretreatment. The basal percentage of cells positive for MHC Class I and II, CD40, and CD152, Fas, and FasL was significantly decreased by estrogen exposure. However, CD8, CD86, CD11b, and CD28 were unaffected by estrogen, and CD80 cell surface staining significantly increased following estrogen exposure. Taken together, these data indicate that estrogen can significantly decrease components of adaptive immunity in microglial cells, and highlight the multi-faceted regulatory effects of estrogen on microglial parameters related to antigen presentation and T cell interaction.

KW - Antigen presentation

KW - Cytokines

KW - Microglial activation

KW - Neuroinflammation

KW - Sex steroids

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JO - Journal of Neuroimmunology

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ER -

Estrogen and brain inflammation: Effects on microglial expression of MHC, costimulatory molecules and cytokines

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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