The emerging role of the cannabinoid receptor family in peripheral and neuro-immune interactions

Current Drug Targets

Volumn 17, Issue 16, 2016, Pages 1834-1840

  Haugh, Orla ^a   Penman, June ^b   Irving, Andrew J ^b,c   Campbell, Veronica A ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

^b UNIVERSITY OF DUNDEE   (United Kingdom)

^c UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

Cannabinoid; Endocannabinoid; GPR18; GPR55; Inflammation; Neurodegeneration; Neuroinflammation

Indexed keywords

ACYLGLYCEROL LIPASE; CANNABINOID RECEPTOR; ENDOCANNABINOID; G PROTEIN COUPLED RECEPTOR;

ALZHEIMER DISEASE; ANTIGEN PRESENTING CELL; CELL INFILTRATION; CELL MIGRATION; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM; HUMAN; IMMUNOMODULATION; MAPK SIGNALING; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROPHYSIOLOGY; PHAGOCYTOSIS; REVIEW; ANIMAL; IMMUNE SYSTEM; METABOLISM; MULTIGENE FAMILY; SIGNAL TRANSDUCTION;

ANIMALS; CENTRAL NERVOUS SYSTEM; HUMANS; IMMUNE SYSTEM; MULTIGENE FAMILY; RECEPTORS, CANNABINOID; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 84982821451     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/1389450117666160112113703     Document Type: Review

References (90)

1. Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003; 4: 873-84.
2. Fowler CJ, Holt S, Nilsson O, Jonsson KO, Tiger G, Jacobsson SOP. The endocannabinoid signaling system: Pharmacological and therapeutic aspects. Pharmacol Biochem Behav 2005; 81: 248-62.
3. Porter AC, Sauer J-M, Knierman MD, et al. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 2002; 301: 1020-4.
4. Sido JM, Nagarkatti PS, Nagarkatti M. Role of endocannabinoid activation of peripheral CB1 receptors in the regulation of autoimmune disease. Int Rev Immunol 2015; 34: 403-14.
5. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1992; 11: 563-83.
6. Pertwee RG, Ross RA. Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fatty Acids 2002; 66: 101-21.
7. Graham ES, Angel CE, Schwarcz LE, Dunbar PR, Glass M. Detailed characterisation of CB2 receptor protein expression in peripheral blood immune cells from healthy human volunteers using flow cytometry. Int J Immunopathol Pharmacol 2010; 23: 25-34.
8. Núñez E, Benito C, Pazos MR, et al. Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study. Synapse 2004; 53: 208-13.
9. Tanasescu R, Constantinescu CS. Cannabinoids and the immune system: An overview. Immunobiology 2010; 215: 588-97.
10. Leleu-Chavain N, Desreumaux P, Chavatte P, Millet R. Therapeutical potential of CB₂ receptors in immune-related diseases. Curr Mol Pharmacol 2013; 6: 183-203.
11. Carrier EJ, Kearn CS, Barkmeier AJ, et al. Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol 2004; 65: 999-1007.
12. Raborn ES, Cabral GA. Cannabinoid inhibition of macrophage migration to the trans-activating (Tat) protein of HIV-1 is linked to the CB(2) cannabinoid receptor. J Pharmacol Exp Ther 2010; 333: 319-27.
13. Han KH, Lim S, Ryu J, et al. CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages. Cardiovasc Res 2009; 84: 378-86.
14. Mai P, Tian L, Yang L, Wang L, Yang L, Li L. Cannabinoid receptor 1 but not 2 mediates macrophage phagocytosis by G(α)i/o/RhoA/ROCK signaling pathway. J Cell Physiol 2015; 230: 1640-50.
15. Jourdan T, Godlewski G, Cinar R, et al. Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Nat Med 2013; 19: 1132-40.
16. Meijerink J, Poland M, Balvers MGJ, et al. Inhibition of COX-2-mediated eicosanoid production plays a major role in the anti-inflammatory effects of the endocannabinoid N-docosahexaenoylethanolamine (DHEA) in macrophages. Br J Pharmacol 2015; 172: 24-37.
17. Alhouayek M, Masquelier J, Cani PD, Lambert DM, Muccioli GG. Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6. Proc Natl Acad Sci USA 2013; 110: 17558-63.
18. Borner C, Hollt V, Kraus J. Activation of human T cells induces upregulation of cannabinoid receptor type 1 transcription. Neuroimmunomodulation 2007; 14: 281-6.
19. Schwarz H, Blanco FJ, Lotz M. Anadamide, an endogenous cannabinoid receptor agonist inhibits lymphocyte proliferation and induces apoptosis. J Neuroimmunol 1994; 55: 107-15.
20. Hegde VL, Hegde S, Cravatt BF, Hofseth LJ, Nagarkatti M, Nagarkatti PS. Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells. Mol Pharmacol 2008; 74: 20-33.
21. Singh UP, Singh NP, Singh B, Price RL, Nagarkatti M, Nagarkatti PS. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10(-/-) mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol Appl Pharmacol 2012; 258: 256-67.
22. Gui H, Liu X, Liu LR, Su DF, Dai SM. Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis. Immunobiology 2015; 220: 817-22.
23. Brinkmann V. FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol 2009; 158: 1173-82.
24. Cencioni MT, Chiurchiù V, Catanzaro G, et al. Anandamide suppresses proliferation and cytokine release from primary human T-lymphocytes mainly via CB2 receptors. PLoS One 2010; 5: e8688.
25. Jackson AR, Nagarkatti P, Nagarkatti M. Anandamide attenuates Th-17 cell-mediated delayed-type hypersensitivity response by triggering IL-10 production and consequent microRNA induction. PLoS One 2014; 9: e93954.
26. Kong W, Li H, Tuma RF, Ganea D. Selective CB2 receptor activation ameliorates EAE by reducing Th17 differentiation and immune cell accumulation in the CNS. Cell Immunol 2014; 287: 1-17.
27. Kozela E, Juknat A, Kaushansky N, Rimmerman N, Ben-Nun A, Vogel Z. Cannabinoids decrease the Th17 inflammatory autoimmune phenotype. J Neuroimmune Pharmacol 2013; 8: 1265-76.
28. Roth MD, Castaneda JT, Kiertscher SM. Exposure to Delta9-tetrahydrocannabinol impairs the differentiation of human monocyte-derived dendritic cells and their capacity for T cell activation. J Neuroimmune Pharmacol 2015; 10: 333-43.
29. Newton CA, Chou P-J, Perkins I, Klein TW. CB(1) and CB(2) cannabinoid receptors mediate different aspects of delta-9-tetrahydrocannabinol (THC)-induced T helper cell shift following immune activation by Legionella pneumophila infection. J Neuroimmune Pharmacol 2009; 4: 92-102.
30. Karmaus PWF, Chen W, Kaplan BLF, Kaminski NE. Δ9-tetrahydrocannabinol suppresses cytotoxic T lymphocyte function independent of CB1 and CB 2, disrupting early activation events. J Neuroimmune Pharmacol 2012; 7: 843-55.
31. Lombard C, Hegde VL, Nagarkatti M, Nagarkatti PS. Perinatal exposure to Δ9-tetrahydrocannabinol triggers profound defects in T cell differentiation and function in fetal and postnatal stages of life, including decreased responsiveness to HIV antigens. J Pharmacol Exp Ther 2011; 339: 607-17.
32. Nakanishi H, Wu Z. Microglia-aging: roles of microglial lysosome-and mitochondria-derived reactive oxygen species in brain aging. Behav Brain Res 2009; 201: 1-7.
33. Walter L, Franklin A, Witting A, et al. Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 2003; 23: 1398-405.
34. Racz I, Nadal X, Alferink J, et al. Interferon-gamma is a critical modulator of CB(2) cannabinoid receptor signaling during neuropathic pain. J Neurosci 2008; 28: 12136-45.
35. Merighi S, Gessi S, Varani K, et al. Cannabinoid CB(2) receptors modulate ERK-1/2 kinase signalling and NO release in microglial cells stimulated with bacterial lipopolysaccharide. Br J Pharmacol 2012; 165: 1773-88.
36. Ramírez BG, Blázquez C, Gómez del Pulgar T, Guzmán M, de Ceballos ML. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 2005; 25: 1904-13.
37. Aso E, Sánchez-Pla A, Vegas-Lozano E, Maldonado R, Ferrer I. Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice. J Alzheimers Dis 2015; 43: 977-91.
38. Schmöle A-C, Lundt R, Ternes S, et al. Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer’s disease mouse model. Neurobiol Aging 2015; 36: 710-9.
39. Koppel J, Vingtdeux V, Marambaud P, et al. CB2 receptor deficiency increases amyloid pathology and alters tau processing in a transgenic mouse model of Alzheimer’s disease. Mol Med 2014; 20: 29-36.
40. Marchalant Y, Brothers HM, Wenk GL. Cannabinoid agonist WIN-55,212-2 partially restores neurogenesis in the aged rat brain. Mol Psychiatry 2009; 14: 1068-9.
41. Ma L, Jia J, Liu X, Bai F, Wang Q, Xiong L. Activation of murine microglial N9 cells is attenuated through cannabinoid receptor CB2 signaling. Biochem Biophys Res Commun 2015; 458: 92-7.
42. Ehrhart J, Obregon D, Mori T, et al. Stimulation of cannabinoid receptor 2 (CB2) supresses microglial activation. J Neuroinflammation 2005; 2: 29.
43. Shao BZ, Wei W, Ke P, Xu ZQ, Zhou JX, Liu C. Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome. CNS Neurosci Ther 2014; 20: 1021-8.
44. Mecha M, Feliú A, Iñigo PM, Mestre L, Carrillo-Salinas FJ, Guaza C. Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors. Neurobiol Dis 2013; 59: 141-50.
45. De Lago E, Moreno-Martet M, Cabranes A, Ramos JA, Fernández-Ruiz J. Cannabinoids ameliorate disease progression in a model of multiple sclerosis in mice, acting preferentially through CB 1 receptor-mediated anti-inflammatory effects. Neuropharmacology 2012; 62: 2298-307.
46. Downer EJ, Clifford E, Gran B, Nel HJ, Fallon PG, Moynagh PN. Identification of the synthetic cannabinoid R(+)WIN55,212-2 as a novel regulator of IFN regulatory factor 3 activation and IFN-beta expression: relevance to therapeutic effects in models of multiple sclerosis. J Biol Chem 2011; 286: 10316-28.
47. Downer EJ, Clifford E, Amu S, Fallon PG, Moynagh PN. The synthetic cannabinoid R(+)WIN55,212-2 augments interferon-β expression via peroxisome proliferator-activated receptor-α. J Biol Chem 2012; 287: 25440-53.
48. Bernal-Chico A, Canedo M, Manterola A, et al. Blockade of monoacylglycerol lipase inhibits oligodendrocyte excitotoxicity and prevents demyelination in vivo. Glia 2015; 63: 163-76.
49. Schicho R, Bashashati M, Bawa M, et al. The atypical cannabinoid O-1602 protects against experimental colitis and inhibits neutrophil recruitment. Inflamm Bowel Dis 2011; 17: 1651-64.
50. Skaper SD, Facci L, Giusti P. Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator. Mol Neurobiol 2013; 48: 340-52.
51. Zhu C, Solorzano C, Sahar S, et al. Proinflammatory stimuli control N-acylphosphatidylethanolamine-specific phospholipase D expression in macrophages. Mol Pharmacol 2011; 79: 786-92.
52. Richardson D, Pearson RG, Kurian N, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 2008; 10: R43.
53. Jean-Gilles L, Feng S, Tench CR, et al. Plasma endocannabinoid levels in multiple sclerosis. J Neurol Sci 2009; 287: 212-5.
54. Cantarella G, Scollo M, Lempereur L, Saccani-Jotti G, Basile F, Bernardini R. Endocannabinoids inhibit release of nerve growth factor by inflammation-activated mast cells. Biochem Pharmacol 2011; 82: 380-8.
55. Santoni G, Cardinali C, Morelli MB, Santoni M, Nabissi M, Amantini C. Danger and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J Neuroinflammation 2015; 12: 21.
56. Wu L-J, Sweet T-B, Clapham DE. International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol Rev 2010; 62: 381-404.
57. Hassan S, Eldeeb K, Millns P, Bennett A, Alexander S, Kendall D. Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br J Pharmacol 2014; 171(9): 2426-39.
58. Clark RB. The role of PPARs in inflammation and immunity. J Leukoc Biol 2002; 71: 388-400.
59. Esposito G, Scuderi C, Valenza M, et al. Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PLoS One 2011; 6: e28668.
60. Aguirre-Rueda D, Guerra-Ojeda S, Aldasoro M, et al. WIN 55,212-2, agonist of cannabinoid receptors, prevents amyloid β1-42 effects on astrocytes in primary culture. PLoS One 2015; 10: e0122843.
61. De Filippis D, Esposito G, Cirillo C, et al. Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. PLoS One 2011; 6: e28159.
62. Brown AJ. Novel cannabinoid receptors. Br J Pharmacol 2007; 152: 567-75.
63. Rao GK, Kaminski NE. Cannabinoid-mediated elevation of intracellular calcium: a structure-activity relationship. J Pharmacol Exp Ther 2006; 317: 820-9.
64. Kaplan BLF, Springs AEB, Kaminski NE. The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT). Biochem Pharmacol 2008; 76: 726-37.
65. Pietr M, Kozela E, Levy R, et al. Differential changes in GPR55 during microglial cell activation. FEBS Lett 2009; 583: 2071-6.
66. Balenga NAB, Aflaki E, Kargl J, et al. GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res 2011; 21: 1452-69.
67. Chiurchiù V, Lanuti M, De Bardi M, Battistini L, Maccorone M. The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells. Int Immunol 2014; 27(3): 153-60.
68. Oka S, Kimura S, Toshida T, Ota R, Yamashita A, Sugiura T. Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells. J Biochem 2010; 147: 671-8.
69. Vassilatis DK, Hohmann JG, Zeng H, et al. The G protein-coupled receptor repertoires of human and mouse. Proc Natl Acad Sci USA 2003; 100: 4903-8.
70. Gantz I, Muraoka A, Yang YK, et al. Cloning and chromosomal localization of a gene (GPR18) encoding a novel seven transmembrane receptor highly expressed in spleen and testis. Genomics 1997; 42: 462-6.
71. Rosenkilde MM, Benned-Jensen T, Andersen H, et al. Molecular pharmacological phenotyping of EBI2: An orphan seven-transmembrane receptor with constitutive activity. J Biol Chem 2006; 281: 13199-208.
72. Kohno M, Hasegawa H, Inoue A, et al. Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18. Biochem Biophys Res Commun 2006; 347: 827-32.
73. McHugh D, Hu SSJ, Rimmerman N, et al. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci 2010; 11: 44.
74. Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T. Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Commun 2007; 362: 928-34.
75. Shore DM, Reggio PH. The therapeutic potential of orphan GPCRs, GPR35 and GPR55. Front Pharmacol 2015; 6: 69.
76. Lu VB, Puhl HL, Ikeda SR. N-Arachidonyl glycine does not activate G protein-coupled receptor 18 signaling via canonical pathways. Mol Pharmacol 2013; 83: 267-82.
77. Alexander SPH. So what do we call GPR18 now? Br J Pharmacol 2012; 165: 2411-3.
78. McHugh D. GPR18 in microglia: implications for the CNS and endocannabinoid system signalling. Br J Pharmacol 2012; 167: 1575-82.
79. McHugh D, Hu SSJ, Rimmerman N, et al. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci 2010; 11: 44.
80. Ryberg E, Larsson N, Sjögren S, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 2007; 152: 1092-101.
81. Rahimi A, Faizi M, Talebi F, Noorbakhsh F, Kahrizi F, Naderi N. Interaction between the protective effects of cannabidiol and palmitoylethanolamide in experimental model of multiple sclerosis in C57BL/6 mice. Neuroscience 2015; 290: 279-87.
82. Borrelli F, Romano B, Petrosino S, et al. Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent. Br J Pharmacol 2015; 172: 142-58.
83. Scuderi C, Esposito G, Blasio A, et al. Palmitoylethanolamide counteracts reactive astrogliosis induced by β -amyloid peptide. J Cell Mol Med 2011; 15: 2664-74.
84. Becker AM, Callahan DJ, Richner JM, et al. GPR18 controls reconstitution of mouse small intestine intraepithelial lymphocytes following bone marrow transplantation. PLoS One 2015; 10: e0133854.
85. Staton PC, Hatcher JP, Walker DJ, et al. The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 2008; 139: 225-36.
86. Malek N, Popiolek-Barczyk K, Mika J, Przewlocka B, Starowicz K. Anandamide, acting via CB2 receptors, alleviates LPS-induced neuroinflammation in rat primary microglial cultures. Neural Plast 2015; 2015: 130639.
87. Kargl J, Balenga N, Parzmair GP, Brown AJ, Heinemann A, Waldhoer M. The cannabinoid receptor CB1 modulates the signaling properties of the lysophosphatidylinositol receptor GPR55. J Biol Chem 2012; 287: 44234-48.
88. Martínez-Pinilla E, Reyes-Resina I, Oñatibia-Astibia A, et al. CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum. Exp Neurol 2014; 261: 44-52.
89. Janefjord E, Mååg JL V, Harvey BS, Smid SD. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell Mol Neurobiol 2013; 34(1): 31-42.
90. Sisay S, Pryce G, Jackson SJ, et al. Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of multiple sclerosis. PLoS One 2013; 8: e76907.