TY - JOUR
T1 - Sativex® effects on promoter methylation and on CNR1/CNR2 expression in peripheral blood mononuclear cells of progressive multiple sclerosis patients
AU - Santoro, Massimo
AU - Mirabella, Massimiliano
AU - De Fino, Chiara
AU - Bianco, Assunta
AU - Lucchini, Matteo
AU - Losavio, Francesco
AU - Sabino, Andrea
AU - Nociti, Viviana
PY - 2017
Y1 - 2017
N2 - Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®. Our cohort included MSS-SP patients, that at the time of Sativex® treatment, are treated (n = 7), not treated (n = 11) or that had terminated interferon-β-1b (IFN-β-1b) therapy (n = 12). By Methylation Sensitive High Resolution Melting (MS-HRM), we characterized the methylation profile of CNR1 and CNR2 promoter region, while the relative mRNA transcript levels of these two genes were evaluated in the same samples by Quantitative Real-Time PCR (qRT-PCR) analysis. We did not find different pattern of cytosine-phosphate-guanine (CpG) methylation in the CNR1/CNR2 promoter region of all MSS-SP patients treated with Sativex®. In addition, CNR1 and CNR2 expression did not significantly differ in MSS-SP patients not treated with IFN-β-1b vs. them that have suspended, while in MSS-SP patients treated with IFN-β-1b during Sativex® therapy we found a specific decrease of the CNR2 expression levels. These results suggest that the different expression of cannabinoid receptors by Sativex® treatment in leukocytes might be regulated through a molecular mechanism that involve interferon modulation.
AB - Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®. Our cohort included MSS-SP patients, that at the time of Sativex® treatment, are treated (n = 7), not treated (n = 11) or that had terminated interferon-β-1b (IFN-β-1b) therapy (n = 12). By Methylation Sensitive High Resolution Melting (MS-HRM), we characterized the methylation profile of CNR1 and CNR2 promoter region, while the relative mRNA transcript levels of these two genes were evaluated in the same samples by Quantitative Real-Time PCR (qRT-PCR) analysis. We did not find different pattern of cytosine-phosphate-guanine (CpG) methylation in the CNR1/CNR2 promoter region of all MSS-SP patients treated with Sativex®. In addition, CNR1 and CNR2 expression did not significantly differ in MSS-SP patients not treated with IFN-β-1b vs. them that have suspended, while in MSS-SP patients treated with IFN-β-1b during Sativex® therapy we found a specific decrease of the CNR2 expression levels. These results suggest that the different expression of cannabinoid receptors by Sativex® treatment in leukocytes might be regulated through a molecular mechanism that involve interferon modulation.
KW - Cannabinoid receptor type 1
KW - Cannabinoid receptor type 2
KW - Interferon-β-1b
KW - Methylation
KW - Neurology
KW - Neurology (clinical)
KW - Sativex®
KW - Cannabinoid receptor type 1
KW - Cannabinoid receptor type 2
KW - Interferon-β-1b
KW - Methylation
KW - Neurology
KW - Neurology (clinical)
KW - Sativex®
UR - https://publicatt.unicatt.it/handle/10807/113515
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85021284977&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85021284977&origin=inward
U2 - 10.1016/j.jns.2017.06.017
DO - 10.1016/j.jns.2017.06.017
M3 - Article
SN - 0022-510X
VL - 379
SP - 298
EP - 303
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - Aug 15
ER -