IFN-beta-regulated genes show abnormal expression in therapy-naïve relapsing-remitting MS mononuclear cells: gene expression analysis employing all reported protein-protein interactions.
The molecular mechanism by which interferon beta (IFN-beta) is effective in treating multiple sclerosis is not well understood. Mononuclear cells from therapy-naïve MS patients, IFN-beta-1b-treated MS patients, and healthy controls were analyzed to examine mRNA changes that characterize both the disease and its treatment. The scientific literature was comprehensively searched for all protein-protein interactions. In MS patients who had never been treated with IFN-beta, statistical analysis revealed coordinate changes in mRNA expression for proteins reported in the literature as "regulated by IFN-beta." As a positive control for this approach, samples from a separate MS patient cohort showed significant change of these same genes during in vivo treatment with IFN-beta-1b.The strength of effect observed for regulation by IFN-beta was greater than for IFN-alpha, IFN-gamma (Th1), or IL-4 (Th2). Of the sets we investigated, the most strongly affected by disease was the subset defined by regulation by both IFN-beta and IFN-alpha. Changes in cells from therapy-naïve MS patients thus anticipated the importance of IFN-beta in therapy. These findings are a significant step towards marrying MS disease etiology and IFN-beta mechanism of action at a molecular level.
Yamaguchi
Ken D
KD
Department of Computational Biology, Bayer HealthCare Pharmaceuticals, 2600 Hilltop Dr., Richmond, CA 94806, USA. ken.yamaguchi@bayer.com
Ruderman
Daniel L
DL
Croze
Ed
E
Wagner
T Charis
TC
Velichko
Sharlene
S
Reder
Anthony T
AT
Salamon
Hugh
H
D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000473:pathology*; D009157:Myasthenia Gravis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013997:Time Factors
D016899:Interferon-beta