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The endogenous cannabinoid anandamide potentiates interleukin‐6 production by astrocytes infected with Theiler's murine encephalomyelitis virus by a receptor‐mediated pathway
Author(s) -
Molina-Holgado Francisco,
Molina-Holgado Eduardo,
Guaza Carmen
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00851-5
Subject(s) - anandamide , cannabinoid receptor , cannabinoid , cannabinoid receptor type 2 , endocannabinoid system , multiple sclerosis , biology , pharmacology , immune system , immunology , receptor , chemistry , antagonist , biochemistry
Theiler's murine encephalomyelitis virus (TMEV) infection of a susceptible strain of mice results in virus persistence in the brain and chronic primary immune‐mediated demyelination, which resembles multiple sclerosis. Recent attention has focused on the anti‐inflammatory and immunosuppressive properties of interleukin‐6, a pleiotropic cytokine involved in the regulation of immunological responses, acute phase protein production and hematopoiesis. Anandamide (arachidonoyl ethanolamine) is a natural brain constituent that binds a specific brain cannabinoid receptor. In this study we investigated whether anandamide can modify interleukin‐6 production by primary cultures of murine brain cortical astrocytes infected with TMEV. Astrocytes from susceptible (SJL/J) and resistant (BALB/c) strains of mice infected with TMEV (10 5 PFU/well) increased IL‐6 release over a period of 24 h. Anandamide caused an enhancement of the release of IL‐6 by TMEV‐infected astrocytes in a concentration‐dependent manner (1–25 μM). Treatment of TMEV‐infected astrocytes with 10 μM arachidonyl trifluoromethyl ketone, a potent inhibitor of the amidase that degrades anandamide, was found to potentiate the effects of anandamide on IL‐6 release. A novel and selective cannabinoid receptor antagonist, SR 141617A, blocked the enhancing effects of anandamide on IL‐6 release by TMEV‐infected astrocytes, suggesting a cannabinoid receptor‐mediated pathway. The physiological implications of these results are unknown, but may be related to the hypothesis of the protective effects of cannabinoids on neurological disorders like multiple sclerosis.