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

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

Publication date: Mar 12, 2019

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-nacEFve 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 Ca homeostasis in endoplasmic reticulum (ER) was also observed. Microfluorimetric analysis confirmed this finding, showing a specific GA effect on ER Ca 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 Ca homeostasis in these cells.

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Criscuolo, C., Cianflone, A., Lanzillo, R., Carrella, D., Carissimo, A., Napolitano, F., de Cegli, R., de Candia, P., La Rocca, C., Petrozziello, T., Matarese, G., Boscia, F., Secondo, A., Di Bernardo, D., and Morra, Brescia. Glatiramer Acetate modulates ion channels expression and calcium homeostasis in B cell of patients with relapsing-remitting multiple sclerosis. 17506. 2019 Sci Rep (9):1.

Concepts Keywords
Apoptosis Autoimmune diseases
Calcium Cytokines
Differential Apoptosis
Endoplasmic Reticulum Relapsing–remitting
ER Multiple sclerosis
Homeostasis Immunotherapy
Immunomodulatory Drug Medical specialties
Ion Channels Glatiramer acetate
Multiple Sclerosis Medicine
Nave Clinical medicine
Phenotype MS
Sci Multiple Sclerosis Treatment
Multiple sclerosis

Semantics

Type Source Name
pathway BSID Reproduction
drug DRUGBANK Antithymocyte immunoglobulin (rabbit)
gene UNIPROT SLC8A3
pathway BSID Aging
disease MESH Aging
gene UNIPROT KCNC4
gene UNIPROT AKT1
gene UNIPROT NGF
disease MESH growth
gene UNIPROT SLC8A1
gene UNIPROT COPE
disease MESH nasal polyps
gene UNIPROT OXCT2
gene UNIPROT RNF31
pathway BSID Platelet activation
disease MESH autoimmunity
gene UNIPROT BRD2
gene UNIPROT AOC2
gene UNIPROT MBNL1
gene UNIPROT COL9A3
gene UNIPROT COMP
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SCN8A
disease MESH Mult
gene UNIPROT EGR3
disease DOID Colon Cancer
disease MESH Colon Cancer
disease MESH Inflammation
disease DOID Colitis
disease MESH Colitis
pathway BSID Gene Expression
gene UNIPROT PROC
gene UNIPROT F11R
gene UNIPROT INTU
gene UNIPROT ZBTB8OS
disease DOID Autoimmune Disease
disease MESH Autoimmune Disease
drug DRUGBANK Formaldehyde
gene UNIPROT ATP8A2
drug DRUGBANK ATP
drug DRUGBANK D-glucose
drug DRUGBANK Dextrose unspecified form
gene UNIPROT DUOXA1
drug DRUGBANK Fluorescein
gene UNIPROT DEGS1
gene UNIPROT NAA50
gene UNIPROT STUB1
gene UNIPROT C2
drug DRUGBANK Streptomycin
gene UNIPROT KIT
disease MESH separated
gene UNIPROT MENT
drug DRUGBANK Trestolone
drug DRUGBANK Mitoxantrone
pathway BSID Oxidative Stress
disease MESH oxidative stress
drug DRUGBANK Nitric Oxide
drug DRUGBANK Ambroxol
drug DRUGBANK Brefeldin A
pathway BSID TRP channels
pathway BSID Release
drug DRUGBANK Potassium Chloride
gene UNIPROT NOVA2
drug DRUGBANK L-Valine
drug DRUGBANK L-Phenylalanine
drug DRUGBANK Aspartame
gene UNIPROT THOP1
gene UNIPROT PTPRF
gene UNIPROT CBLIF
gene UNIPROT CD19
gene UNIPROT CDK2
disease MESH death
drug DRUGBANK L-Tyrosine
gene UNIPROT CA2
gene UNIPROT TRPC4
gene UNIPROT TRPC3
gene UNIPROT TRPV2
gene UNIPROT TRPC1
gene UNIPROT TYRP1
drug DRUGBANK L-Tryptophan
drug DRUGBANK Naltrexone
drug DRUGBANK Vigabatrin
disease MESH relapses
drug DRUGBANK Corticosterone
drug DRUGBANK Estradiol
pathway BSID Translation
gene UNIPROT NES
disease MESH multiple
drug DRUGBANK Coenzyme M
pathway BSID Apoptosis
gene UNIPROT SET
disease DOID multiple sclerosis
disease MESH multiple sclerosis
pathway BSID Immune System
gene UNIPROT DEPP1
gene UNIPROT GOPC
gene UNIPROT CEP55
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH communities
gene UNIPROT CST7
gene UNIPROT SGSM3
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
gene UNIPROT CNR1
drug DRUGBANK Ocrelizumab
gene UNIPROT NR4A2
gene UNIPROT ALG3
disease DOID relapsing-remitting multiple sclerosis
disease MESH relapsing-remitting multiple sclerosis
drug DRUGBANK Calcium
drug DRUGBANK Glatiramer

Original Article

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