title: The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells.
abstract: Endocannabinoids are released after brain injury and believed to attenuate neuronal damage by binding to CB(1) receptors and protecting against excitotoxicity. Such excitotoxic brain lesions initially result in primary destruction of brain parenchyma, which attracts macrophages and microglia. These inflammatory cells release toxic cytokines and free radicals, resulting in secondary neuronal damage. In this study, we show that the endocannabinoid system is highly activated during CNS inflammation and that the endocannabinoid anandamide (AEA) protects neurons from inflammatory damage by CB(1/2) receptor-mediated rapid induction of mitogen-activated protein kinase phosphatase-1 (MKP-1) in microglial cells associated with histone H3 phoshorylation of the mkp-1 gene sequence. As a result, AEA-induced rapid MKP-1 expression switches off MAPK signal transduction in microglial cells activated by stimulation of pattern recognition receptors. The release of AEA in injured CNS tissue might therefore represent a new mechanism of neuro-immune communication during CNS injury, which controls and limits immune response after primary CNS damage.
authors.affiliation: Institute of Immunology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Eljaschewitsch
authors.forename: Anke
authors.initials: A
authors.lastname: Witting
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Thomas
authors.initials: T
authors.lastname: Lee
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schmidt
authors.forename: Susanne
authors.initials: S
authors.lastname: Wolf
authors.forename: Heide
authors.initials: H
authors.lastname: Hoertnagl
authors.forename: Cedric S
authors.initials: CS
authors.lastname: Raine
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
authors.forename: Oliver
authors.initials: O
authors.lastname: Ullrich
mesh_terms: D000328:Adult; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism* / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002470:Cell Survival; D002478:Cells, Cultured; D054638:Dual Specificity Phosphatase 1; D004660:Encephalitis / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D063388:Endocannabinoids; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D053284:Polyunsaturated Alkamides; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D018797:Cell Cycle Proteins; D063388:Endocannabinoids; D017874:Immediate-Early Proteins; D018696:Neuroprotective Agents; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D048049:Extracellular Signal-Regulated MAP Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; C078814:anandamide