Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis.
Understanding the mechanisms that sustain the effects of disease modifying drugs in multiple sclerosis (MS) may help refine current therapies and improve our knowledge of disease pathogenesis. By using cDNA microarrays, we investigated gene expression in the peripheral blood mononuclear cells (PBMC) of 7 MS patients, at baseline (T0) as well as after 1 (T1) and 3 months (T3) of interferon beta-1a (IFN-beta-1a; Rebif 44 microg) therapy. Gene expression changes involved genes of both immunological and non-immunological significance. We validated IL-10 up-regulation, which is in accordance with previous reports, and other novel changes that underscore the capacity of IFN-beta to impair antigen presentation and migration of inflammatory elements into the central nervous system (up-regulation of filamin B and down-regulation of IL-16 and rab7). Overall, gene expression changes became less pronounced after 3 months of therapy, suggesting a homeostatic response to IFN-beta. This may be of use for the design of new treatment schedules.
Annibali
Viviana
V
Department of Neurology and Center for Experimental Neurological Therapy, S Andrea Hospital, University of Rome La Sapienza, Rome, Italy.
Di Giovanni
Simone
S
Cannoni
Stefania
S
Giugni
Elisabetta
E
Bomprezzi
Roberto
R
Mattei
Carlo
C
Elkahloun
Abdel
A
Coccia
Eliana Marina
EM
Alfò
Marco
M
Orzi
Francesco
F
Ristori
Giovanni
G
Salvetti
Marco
M
D000328:Adult; D003285:Contractile Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005260:Female; D064448:Filamins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019410:Interleukin-16 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000090802:rab7 GTP-Binding Proteins
D003285:Contractile Proteins; D064448:Filamins; D019410:Interleukin-16; D008840:Microfilament Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D016753:Interleukin-10; D016899:Interferon-beta; D020691:rab GTP-Binding Proteins; D000068556:Interferon beta-1a