Unraveling Natalizumab Effects on Deregulated miR-17 Expression in CD4+ T Cells of Patients with Relapsing-Remitting Multiple Sclerosis

Autor: Maria Meira, Ludwig Kappos, Tobias Derfuss, Claudia Sievers, Maria Rasenack, Francine Hoffmann, Jens Kuhle, Raija L.P. Lindberg
Jazyk: angličtina
Rok vydání: 2014
Předmět:
CD4-Positive T-Lymphocytes
Male
Lymphocyte Activation
Natalizumab
Cell Movement
Immunology and Allergy
Regulation of gene expression
Bcl-2-Like Protein 11
Cell Cycle
General Medicine
Middle Aged
Cell cycle
medicine.anatomical_structure
Female
Signal Transduction
Research Article
medicine.drug
Adult
Cyclin-Dependent Kinase Inhibitor p21
lcsh:Immunologic diseases. Allergy
Article Subject
T cell
Immunology
Protein Serine-Threonine Kinases
Biology
Antibodies
Monoclonal
Humanized
Multiple Sclerosis
Relapsing-Remitting
Downregulation and upregulation
Proto-Oncogene Proteins
microRNA
medicine
Humans
PTEN
Cell Proliferation
Multiple sclerosis
PTEN Phosphohydrolase
Receptor
Transforming Growth Factor-beta Type II
Membrane Proteins
medicine.disease
MicroRNAs
Gene Expression Regulation
Case-Control Studies
Cell Migration Inhibition
Cancer research
biology.protein
Apoptosis Regulatory Proteins
lcsh:RC581-607
Receptors
Transforming Growth Factor beta
E2F1 Transcription Factor
Zdroj: Journal of Immunology Research, Vol 2014 (2014)
Journal of Immunology Research
ISSN: 2314-8861
DOI: 10.1155/2014/897249
Popis: MicroRNAs (miRNAs) are a family of noncoding RNAs that play critical roles in the posttranscriptional regulation of gene expression. Accumulating evidence supports their involvement in the pathogenesis of multiple sclerosis (MS). Here, we compare miR-17 expressions in CD4+T cells from relapsing-remitting (RR) MS patients treated with natalizumab versus untreated patients. miR-17 was downregulated under natalizumab treatment and upregulated during relapse, therefore supporting a possible role of miR-17 in MS immunopathogenesis. Downregulation of miR-17 was associated with upregulation of PTEN, BIM, E2F1, and p21 target genes.In vitromiR-17 inhibition was associated with upregulation of the same targets and resulted in impaired CD4+T cell activation and proliferation. We further describe deregulated TGFBR2 expression in untreated patients versus healthy volunteers (HVs) and confirmin vitrothe link between miR-17 and TGFBR2 expressions. These findings support an effect of natalizumab on expression of specific miRNA and subsequent expression of genes involved in proliferation and control of the cell cycle.
Databáze: OpenAIRE
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