Microarray analysis identifies an aberrant expression of apoptosis and DNA damage-regulatory genes in multiple sclerosis

• Published in: Neurobiology of disease Vol. 18; no. 3; pp. 537 - 550
• Main Authors: Satoh, Jun-ichi, Nakanishi, Megumi, Koike, Fumiko, Miyake, Sachiko, Yamamoto, Toshiyuki, Kawai, Mitsuru, Kikuchi, Seiji, Nomura, Kyouichi, Yokoyama, Kazumasa, Ota, Kohei, Kanda, Takashi, Fukazawa, Toshiyuki, Yamamura, Takashi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2005; Elsevier
• Subjects: Adult; Apoptosis; Apoptosis - physiology; DNA Damage - genetics; Down-Regulation - genetics; Female; Gene expression profile; Gene Expression Profiling - methods; Gene Expression Profiling - statistics & numerical data; Humans; Male; Microarray; Middle Aged; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Oligonucleotide Array Sequence Analysis - methods; Oligonucleotide Array Sequence Analysis - statistics & numerical data; Up-Regulation - genetics; Multiple sclerosis; Microarray; Apoptosis; Gene expression profile
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2004.10.007

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.