title: Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells.
abstract: We performed microarray analysis of peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients and detected a profile of immune cell activation, autoantigen upregulation, and enhanced E2F pathway transcription. Accordingly, E2f1-deficient mice manifested only mild disability upon induction of experimental autoimmune encephalomyelitis (EAE). Furthermore, PBMCs from Avonex-treated patients had lower expression of E2F targets. The profile was enriched in genes known to harbor MS-associated polymorphisms, or localized to MS susceptibility chromosomal regions. Our study shows that PBMC microarrays reflect MS pathobiology that can be validated in the EAE model.
authors.affiliation: Laboratory of Transcriptional and Immune Regulation, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02139, USA.
authors.forename: Antonio H
authors.initials: AH
authors.lastname: Iglesias
authors.forename: Sandra
authors.initials: S
authors.lastname: Camelo
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Raul
authors.initials: R
authors.lastname: Villanueva
authors.forename: George
authors.initials: G
authors.lastname: Stephanopoulos
authors.forename: Fernando
authors.initials: F
authors.lastname: Dangond
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D005810:Multigene Family / Q000187:drug effects; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D014157:Transcription Factors; D016899:Interferon-beta; D000068556:Interferon beta-1a