Anandamide suppresses nitric oxide and TNF-alpha responses to Theiler's virus or endotoxin in astrocytes.
Astrocytes are an important cell population in the CNS, involved in cytokine homeostasis and participating in a variety of important physiological and pathological processes. In the present study we showed that primary cultures of neonatal mouse cortical astrocytes stimulated with lipopolysaccharide (Balb/c mice strain, LPS: 1 microgram/ml, 18 h) or Theiler's virus, TMEV (SJL/J mice strain, TMEV: 10(5) PFU/well, 24 h) released an increased amount of nitrites (NO2-) and tumour necrosis factor-alpha (TNF-alpha) into the culture medium. Exogenous cannabinoids are known to modulate the function of immune cells. Anandamide, an endogenous ligand for the cannabinoid receptor, blocked the release of NO2- and TNF-alpha induced by LPS in a dose-dependent manner. In TMEV-stimulated astrocytes anandamide also suppressed, in a dose-related manner, the stimulatory effects of TMEV on both NO2- and TNF-alpha. It is suggested that anandamide exerts an immunoregulatory role in the CNS. These results could have important implications in the modulation of immunological and inflammatory processes by cannabinoid agents.
Molina-Holgado
F
F
Neural Plasticity Unit, Instituto Cajal, CSIC, Madrid, Spain.
Lledó
A
A
Guaza
C
C
D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D063388:Endocannabinoids; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D010850:Picornaviridae Infections / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001095:Arachidonic Acids; D063388:Endocannabinoids; D004731:Endotoxins; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; C078814:anandamide