title: Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis.
abstract: To clarify the molecular mechanisms underlying multiple sclerosis (MS)-promoting autoimmune process, we have investigated a comprehensive gene expression profile of T cell and non-T cell fractions of peripheral blood mononuclear cells (PBMC) isolated from 72 MS patients and 22 age- and sex-matched healthy control (CN) subjects by using a cDNA microarray. Among 1258 genes examined, 173 genes in T cells and 50 genes in non-T cells were expressed differentially between MS and CN groups. Downregulated genes greatly outnumbered upregulated genes in MS. More than 80% of the top 30 most significant genes were categorized into apoptosis signaling-related genes of both proapoptotic and antiapoptotic classes. They included upregulation in MS of orphan nuclear receptor Nurr1 (NR4A2), receptor-interacting serine/threonine kinase 2 (RIPK2), and silencer of death domains (SODD), and downregulation in MS of TNF-related apoptosis-inducing ligand (TRAIL), B-cell CLL/lymphoma 2 (BCL2), and death-associated protein 6 (DAXX). Furthermore, a set of the genes involved in DNA repair, replication, and chromatin remodeling was downregulated in MS. These results suggest that MS lymphocytes show a complex pattern of gene regulation that represents a counterbalance between promoting and preventing apoptosis and DNA damage of lymphocytes.
authors.affiliation: Department of Immunology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Satoh
authors.forename: Megumi
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Koike
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawai
authors.forename: Seiji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Kyouichi
authors.initials: K
authors.lastname: Nomura
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Kohei
authors.initials: K
authors.lastname: Ota
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D015854:Up-Regulation / Q000235:genetics