COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependentmanner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines fromnormal healthy subjects and patients with relapsing-remittingmultiple sclerosis (MS). InMS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanisminvolving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines. COR167 was also able to reduce in vitro migration of stimulated immunocompetent cells through human brain endothelium associated with a significant reduction of levels of several chemokines. These findings demonstrate that COR167 exerts potent immunomodulatory effects and confirm the cannabinoid CB2 receptor as a novel pharmacological target to counteract neuroinflammation.
Annunziata, P., Cioni, C., Mugnaini, C., Corelli, F. (2017). Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis. JOURNAL OF NEUROIMMUNOLOGY, 303, 66-74.
Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis.
ANNUNZIATA, PASQUALE;CIONI, CHIARA;MUGNAINI, CLAUDIA;CORELLI, FEDERICO
2017-01-01
Abstract
COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependentmanner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines fromnormal healthy subjects and patients with relapsing-remittingmultiple sclerosis (MS). InMS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanisminvolving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines. COR167 was also able to reduce in vitro migration of stimulated immunocompetent cells through human brain endothelium associated with a significant reduction of levels of several chemokines. These findings demonstrate that COR167 exerts potent immunomodulatory effects and confirm the cannabinoid CB2 receptor as a novel pharmacological target to counteract neuroinflammation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/1006789
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