title: Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis.
abstract: Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and -17, interferon-gamma and associated downstream pathways. Comparison of two poles of MS pathology--acute lesions with inflammation versus 'silent' lesions without inflammation--revealed differentially transcribed genes. Some products of these genes were chosen as targets for therapy of experimental autoimmune encephalomyelitis (EAE) in mice. Granulocyte colony-stimulating factor is upregulated in acute, but not in chronic, MS lesions, and the effect on ameliorating EAE is more pronounced in the acute phase, in contrast to knocking out the immunoglobulin Fc receptor common gamma chain where the effect is greatest on chronic disease. These results in EAE corroborate the microarray studies on MS lesions. Large-scale analysis of transcripts in MS lesions elucidates new aspects of pathology and opens possibilities for therapy.
authors: Department of Neurology and Neurological Sciences, Beckman Center, Stanford University, Stanford, California, USA.
authors: Christopher
authors: C
authors: Lock
authors: Guy
authors: G
authors: Hermans
authors: Rosetta
authors: R
authors: Pedotti
authors: Andrea
authors: A
authors: Brendolan
authors: Eric
authors: E
authors: Schadt
authors: Hideki
authors: H
authors: Garren
authors: Annette
authors: A
authors: Langer-Gould
authors: Samuel
authors: S
authors: Strober
authors: Barbara
authors: B
authors: Cannella
authors: John
authors: J
authors: Allard
authors: Paul
authors: P
authors: Klonowski
authors: Angela
authors: A
authors: Austin
authors: Nagin
authors: N
authors: Lad
authors: Naftali
authors: N
authors: Kaminski
authors: Stephen J
authors: SJ
authors: Galli
authors: Jorge R
authors: JR
authors: Oksenberg
authors: Cedric S
authors: CS
authors: Raine
authors: Renu
authors: R
authors: Heller
authors: Lawrence
authors: L
authors: Steinman
mesh_terms: D000208:Acute Disease; D000818:Animals; D001344:Autopsy; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics*; D020381:Interleukin-17 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011961:Receptors, Fc / Q000502:physiology; D015203:Reproducibility of Results; D014158:Transcription, Genetic
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D011961:Receptors, Fc; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma