title: 17Beta-estradiol treatment profoundly down-regulates gene expression in spinal cord tissue in mice protected from experimental autoimmune encephalomyelitis.
abstract: It is now well documented that experimental autoimmune encephalomyelitis (EAE) can be effectively prevented by estrogen therapy. Previously, we identified a limited set of genes that were altered in spleens of mice protected from EAE by 17beta-estradiol (E2) treatment. As a continuation of these studies, we present here transcriptional changes in genes expressed in spinal cord tissue. The Affymetrix microarray system was used to screen more than 12,000 genes from E2-treated double transgenic (BV8S2 and AV4) female mice protected from EAE vs. control mice with severe EAE. We found that estrogen therapy had a profound inhibitory effect on the expressions of many immune-related genes in spinal cords. Estrogen significantly affected the transcription of 315 genes, 302 of which were down-regulated and only 13 that were up-regulated by > or = 2.4 fold. A number of genes encoding the histocompatibility complex, cytokines/receptors, chemokines, adhesion molecules, and signal transduction proteins were strongly down-regulated (> 20 fold) in estrogen-treated mice to levels similar to those of the spinal cord tissue from unmanipulated mice. The identification of genes with altered expression patterns in the spinal cords of estrogen-treated mice provides unique insight into the process that ultimately results in protection against EAE.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97201, USA.
authors.forename: Agata
authors.initials: A
authors.lastname: Matejuk
authors.forename: Jami
authors.initials: J
authors.lastname: Dwyer
authors.forename: Corwyn
authors.initials: C
authors.lastname: Hopke
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D004958:Estradiol