TY - JOUR
T1 - Evaluation of the effects of 17β-estradiol (17β-E2) on gene expression in experimental autoimmune encephalomyelitis using DNA microarray
AU - Matejuk, Agata
AU - Dwyer, Jami
AU - Zamora, Alex
AU - Vandenbark, Arthur A.
AU - Offner, Halina
PY - 2002
Y1 - 2002
N2 - The aim of this study was to identify immune-related genes affected by treatment with 17β-estradiol (17β-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 TNFα (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), TGF β3, IL-18, and two interferon-γ-induced genes, the chemokines: monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β), vascular cell adhesion molecule (VCAM), and disintegrin metalloprotease (thought to regulate TNFα 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.
AB - The aim of this study was to identify immune-related genes affected by treatment with 17β-estradiol (17β-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 TNFα (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), TGF β3, IL-18, and two interferon-γ-induced genes, the chemokines: monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β), vascular cell adhesion molecule (VCAM), and disintegrin metalloprotease (thought to regulate TNFα 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.
UR - http://www.scopus.com/inward/record.url?scp=85047682175&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047682175&partnerID=8YFLogxK
U2 - 10.1210/endo.143.1.8571
DO - 10.1210/endo.143.1.8571
M3 - Article
C2 - 11751623
AN - SCOPUS:85047682175
SN - 0013-7227
VL - 143
SP - 313
EP - 319
JO - Endocrinology
JF - Endocrinology
IS - 1
ER -