Glatiramer Acetate modulates ion channels expression and calcium homeostasis in B cell of patients with relapsing-remitting multiple sclerosis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

C. Criscuolo, A. Cianflone, R. Lanzillo, D. Carrella, A. Carissimo, F. Napolitano, R. de Cegli, P. de Candia, C. La Rocca, T. Petrozziello, G. Matarese, F. Boscia, A. Secondo, D. Di Bernardo, V. Brescia Morra

ABSTRACT

To investigate the effects of Glatiramer Acetate (GA) on B cells by an integrated computational and experimental approach. GA is an immunomodulatory drug approved for the treatment of multiple sclerosis (MS). GA effect on B cells is yet to be fully elucidated. We compared transcriptional profiles of B cells from treatment-naïve relapsing remitting MS patients, treated or not with GA for 6 hours in vitro, and of B cells before and after six months of GA administration in vivo. Microarrays were analyzed with two different computational approaches, one for functional analysis of pathways (Gene Set Enrichment Analysis) and one for the identification of new drug targets (Mode-of-action by Network Analysis). GA modulates the expression of genes involved in immune response and apoptosis. A differential expression of genes encoding ion channels, mostly regulating Ca2+ homeostasis in endoplasmic reticulum (ER) was also observed. Microfluorimetric analysis confirmed this finding, showing a specific GA effect on ER Ca2+ concentration. Our findings unveils a GA regulatory effect on the immune response by influencing B cell phenotype and function. In particular, our results highlight a new functional role for GA in modulating Ca2+ homeostasis in these cells. More... »

PAGES

4208

References to SciGraph publications

  • 2004-05. Mitoxantrone in CNS DRUGS
  • 2012-07. Ion channels and transporters in lymphocyte function and immunity in NATURE REVIEWS IMMUNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-38152-8

    DOI

    http://dx.doi.org/10.1038/s41598-018-38152-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112706449

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30862866


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