Suppression of immune system genes by methylprednisolone in exacerbations of multiple sclerosis. Preliminary results.
Acute relapses of multiple sclerosis (MS) are treated with intravenous methylprednisolone (IVMP), which speeds recovery from exacerbation. It is known that IVMP suppresses the immunological activation which occurs during an acute attack of MS. However, the specific target genes affected by this therapy remain obscure. A cDNA microarray for 448 genes was used to identify the target genes in IVMP therapy. Total RNA was isolated from peripheral blood mononuclear cells derived from six MS patients immediately before and after completion of therapy. IVMP significantly reduced mRNA levels for T-cell-specific transcription factor 7 (p=0.02), T-cell-specific protein-tyrosine kinase (p=0.02), T-cell surface glycoprotein CD5 (p=0.05) and interferon-stimulated gene factor 3 gamma subunit (p=0.04). Significantly increased expression was found for eosinophil-derived neurotoxin (p=0.05). The suppression of expression of genes associated with T-cell differentiation and antigen-specific T-cell activation detected in this study may contribute to the beneficial effect of MP in relapses of MS.
Airla
Nina
N
Tampere University Hospital, Centre for Laboratory Medicine, Laboratory of Atherosclerosis Genetics Finn-Medi 2, 3rd Floor, P. O. Box 2000, 33521 Tampere, Finland. nina.airla@uta.fi
Luomala
Mari
M
Elovaara
Irina
I
Kettunen
Eeva
E
Knuutila
Sakari
S
Lehtimäki
Terho
T
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018956:CD5 Antigens / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D047208:Eosinophil-Derived Neurotoxin / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007107:Immune System / Q000187:drug effects; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D051821:Lymphoid Enhancer-Binding Factor 1; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012313:RNA / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D000893:Anti-Inflammatory Agents; D018956:CD5 Antigens; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D051821:Lymphoid Enhancer-Binding Factor 1; D014157:Transcription Factors; D012313:RNA; D011505:Protein-Tyrosine Kinases; D047208:Eosinophil-Derived Neurotoxin; D008775:Methylprednisolone