PMID- 11751623 OWN - NLM STAT- MEDLINE DCOM- 20020117 LR - 20131121 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 143 IP - 1 DP - 2002 Jan TI - Evaluation of the effects of 17beta-estradiol (17beta-e2) on gene expression in experimental autoimmune encephalomyelitis using DNA microarray. PG - 313-9 AB - The aim of this study was to identify immune-related genes affected by treatment with 17beta-estradiol (17beta-E2) that contribute to protection of T cell antigen receptor double transgenic mice from experimental autoimmune encephalomyelitis (EAE). The Affymetrix microarray system was used to screen more than 12,000 genes from E2-treated mice protected from EAE vs. control mice with severe EAE. In general, E2 treatment affected about 10% of the genes tested, but only 18 cytokine, chemokine/receptor, adhesion molecule, or activation genes were up- or down-regulated more than 2.4-fold by E2 treatment. Down-regulated genes included TNFalpha (an important proinflammatory cytokine in EAE); peptidoglycan recognition proteins (Pgrp); regulated on activation, normal T cell expressed and secreted (RANTES); and neural cell adhesion molecule (MCP-1). Up-regulated genes included cytotoxic T lymphocyte antigen-4 (CTLA-4; known to inhibit T cell activation), TGFbeta3, IL-18, and two interferon-gamma-induced genes, the chemokines: monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta), vascular cell adhesion molecule (VCAM), and disintegrin metalloprotease (thought to regulate TNFalpha production). These results implicate a limited set of known and previously unsuspected E2-sensitive genes that may be crucial for inhibition of EAE and potentially the human disease, multiple sclerosis. FAU - Matejuk, Agata AU - Matejuk A AD - Department of Neurology, Oregon Health Sciences University, Portland, OR 97201, USA. FAU - Dwyer, Jami AU - Dwyer J FAU - Zamora, Alex AU - Zamora A FAU - Vandenbark, Arthur A AU - Vandenbark AA FAU - Offner, Halina AU - Offner H LA - eng GR - AI-42376/AI/NIAID NIH HHS/United States GR - NS-23221/NS/NINDS NIH HHS/United States GR - NS-23444/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 4TI98Z838E (Estradiol) RN - 9007-81-2 (Freund's Adjuvant) RN - EC 3.1.- (Ribonucleases) SB - IM MH - Animals MH - Encephalomyelitis, Autoimmune, Experimental/*genetics MH - Estradiol/*pharmacology MH - Female MH - Freund's Adjuvant/pharmacology MH - Gene Expression/*drug effects MH - Mice MH - Mice, Transgenic MH - Nuclease Protection Assays MH - Oligonucleotide Array Sequence Analysis MH - Ribonucleases EDAT- 2001/12/26 10:00 MHDA- 2002/01/18 10:01 CRDT- 2001/12/26 10:00 PHST- 2001/12/26 10:00 [pubmed] PHST- 2002/01/18 10:01 [medline] PHST- 2001/12/26 10:00 [entrez] AID - 10.1210/endo.143.1.8571 [doi] PST - ppublish SO - Endocrinology. 2002 Jan;143(1):313-9. doi: 10.1210/endo.143.1.8571.