Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 2005 Oct;95(2):437-45
Date
08/10/2005Pubmed ID
16086683DOI
10.1111/j.1471-4159.2005.03380.xScopus ID
2-s2.0-26844448746 (requires institutional sign-in at Scopus site) 407 CitationsAbstract
The cannabinoid system is known to be important in neuronal regulation, but is also capable of modulating immune function. Although the CNS resident microglial cells have been shown to express the CB2 subtype of cannabinoid receptor during non-immune-mediated pathological conditions, little is known about the expression of the cannabinoid system during immune-mediated CNS pathology. To examine this question, we measured CB2 receptor mRNA expression in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) and, by real-time PCR, found a 100-fold increase in CB2 receptor mRNA expression during EAE onset. We next determined whether microglial cells specifically express the CB2 receptor during EAE, and found that activated microglial cells expressed 10-fold more CB2 receptor than microglia in the resting state. To determine the signals required for the up-regulation of the CB2 receptor, we cultured microglial cells with combinations of gamma-interferon (IFN-gamma) and granulocyte) macrophage-colony stimulating factor (GM-CSF), which both promote microglial cell activation and are expressed in the CNS during EAE, and found that they synergized, resulting in an eight to 10-fold increase in the CB2 receptor. We found no difference in the amount of the CB2 receptor ligand, 2-arachidonylglycerol (2-AG), in the spinal cord during EAE. These data demonstrate that microglial cell activation is accompanied by CB2 receptor up-regulation, suggesting that this receptor plays an important role in microglial cell function in the CNS during autoimmune-induced inflammation.
Author List
Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BNAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArachidonic Acid
Bone Marrow Cells
Cells, Cultured
Cytokines
DNA, Complementary
Encephalomyelitis, Autoimmune, Experimental
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor
Inflammation
Interferon-gamma
Macrophage Activation
Macrophages
Mass Spectrometry
Mice
Mice, Inbred C57BL
Microglia
RNA, Messenger
Receptor, Cannabinoid, CB2
Recombinant Fusion Proteins
Reverse Transcriptase Polymerase Chain Reaction
Spinal Cord
Up-Regulation
