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 17beta-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17beta-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 ERalpha and ERbeta, were examined in N9 microglial cells. Additionally, the effects of 17beta-estradiol on basal and LPS-induced release of cytokines (TNF-alpha, IFN-gamma, IL-2, IL-4, and IL-10) were determined. Data indicate that estrogen increases IL-10 while decreasing TNFalpha and IFNgamma 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.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, MN 222 Chandler Medical Center, Lexington, KY 40536-0298, USA.
authors.forename: Filomena O
authors.initials: FO
authors.lastname: Dimayuga
authors.forename: Janelle L
authors.initials: JL
authors.lastname: Reed
authors.forename: Genevieve A
authors.initials: GA
authors.lastname: Carnero
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.forename: Edgardo R
authors.initials: ER
authors.lastname: Dimayuga
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Dimayuga
authors.forename: Andrea
authors.initials: A
authors.lastname: Perger
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Wilson
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keller
authors.forename: Annadora J
authors.initials: AJ
authors.lastname: Bruce-Keller
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004660:Encephalitis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004958:Estradiol / Q000494:pharmacology*; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000187:drug effects*; D005805:Genes, MHC Class I / Q000502:physiology*; D005802:Genes, MHC Class II / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011946:Receptors, Antigen / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011946:Receptors, Antigen; D018121:Receptors, Cytokine; D011960:Receptors, Estrogen; D004958:Estradiol