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Natalizumab therapy modulates miR-155, miR-26a and proinflammatory cytokine expression in MS patients

Mameli, Giuseppe and Arru, Giannina and Caggiu, Elisa and Niegowska, Magdalena and Leoni, Stefania and Madeddu, Giordano and Babudieri, Sergio and Sechi, Gianpietro and Sechi, Leonardo Antonio (2016) Natalizumab therapy modulates miR-155, miR-26a and proinflammatory cytokine expression in MS patients. PLoS One, Vol. 11 (6), e0157153. ISSN 1932-6203. Article.

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DOI: 10.1371/journal.pone.0157153

Abstract

MicroRNAs fine-tune the regulation of Th1/Th17 lymphocyte subsets in multiple sclerosis. We investigated the expression of miRNAs (previously associated with mycobacterial and viral infections) in MS patients and healthy donors (HD) following 6 months natalizumab therapy. In addition, Th1/Th17 cytokines and the presence of anti-EBNA1/VCA IgG in MS patients with different pattern of miRNA expression have been evaluated. MiR-155, miR-26a, miR-132, miR-146a and Th1/Th17 cytokines expression was detected by RT-real time PCR; moreover anti-EBNA1 and VCA IgG titres were measured by ELISA. We observed an up-regulation of miR-155 (p value = 0.009) and miR-132 (p value = 0.04) in MS patients compared to HD. In MS patients, IL-17a (p = 0.037), IFN γ (p = 0.012) and TNFα (p = 0.015) but not IL-6 were over-expressed compared to HD. Two different miRNAs patterns associated to the expression of different cytokines were observed in the MS cohort. Moreover, a down-regulation of miR-155 and miR-26a was seen in MS patients during and after natalizumab therapy. MS patients that over-expressed miR-155 showed a higher EBNA1 IgG titer than MS patients with high levels of miR-26a. In conclusions the expression of particular miRNAs modulates the pro-inflammatory cytokine expression and the humoral response against EBV and this expression is natalizumab regulated.

Item Type:Article
ID Code:11324
Status:Published
Refereed:Yes
Uncontrolled Keywords:Multiple sclerosis, microRNAs, cytokines, cytokine therapy, gene expression, enzyme-linked immunoassays, immune response, polymerase chain reaction
Subjects:Area 06 - Scienze mediche > MED/17 Malattie infettive
Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Area 06 - Scienze mediche > MED/26 Neurologia
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Medicina Clinica e Sperimentale
Publisher:Public Library of Science
ISSN:1932-6203
Copyright Holders:© 2016 Mameli et al.
Deposited On:10 Apr 2017 14:22

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