Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

Mediators of Inflammation

Volumn 2016, Issue , 2016, Pages

  Mccoy, Kathleen L ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA INTERFERON; CANNABINOID; CANNABINOID RECEPTOR; CYTOKINE; ENDOCANNABINOID; ICOSANOID; LIGAND; MITOGEN ACTIVATED PROTEIN KINASE; MYELOID DIFFERENTIATION FACTOR 88; PATHOGEN ASSOCIATED MOLECULAR PATTERN; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR ADAPTOR MOLECULE 1;

BIOSYNTHESIS; CELL ACTIVATION; CYTOKINE PRODUCTION; HOMEOSTASIS; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; INFLAMMATION; INNATE IMMUNITY; METABOLISM; MICROGLIA; NONHUMAN; PROTEIN FAMILY; PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; ANIMAL;

ANIMALS; CANNABINOIDS; HUMANS; IMMUNITY, INNATE; INFLAMMATION; TOLL-LIKE RECEPTORS;

EID: 84983784415     PISSN: 09629351     EISSN: 14661861     Source Type: Journal    
DOI: 10.1155/2016/5831315     Document Type: Review

References (150)

1. M. Ben Amar, "Cannabinoids in medicine: a review of their therapeutic potential," Journal of Ethnopharmacology, vol. 105, no. 1-2, pp. 1-25, 2006.
2. K. Mackie, "Cannabinoid receptors as therapeutic targets," Annual Review of Pharmacology and Toxicology, vol. 46,pp. 101-122, 2006.
3. V. DiMarzo and L. De Petrocellis, "Plant, synthetic, and endogenous cannabinoids in medicine," Annual Review of Medicine, vol. 57, pp. 553-574, 2006.
4. J. L. Croxford and T. Yamamura, "Cannabinoids and the immune system: potential for the treatment of inflammatory diseases" Journal of Neuroimmunology, vol. 166, no. 1-2, pp. 3-18, 2005.
5. "Marijuana abuse," NIDA Research Report Series NIH Publication No. 05-3859, 2005.
6. M. W. Zhang and R. C. Ho, "The cannabis dilemma: a review of its associated risks and clinical efficacy," Journal of Addiction, vol. 2015, Article ID707596, 6 pages, 2015.
7. E. J. Rahn and A. G. Hohmann, "Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside," Neurotherapeutics, vol. 6, no. 4, pp. 713-737, 2009.
8. R. G. Pertwee, "Emerging strategies for exploiting cannabinoid receptor agonists as medicines," British Journal of Pharmacology, vol. 156, no. 3, pp. 397-411, 2009.
9. Y. Y. Syed,K. McKeage, and L. J. Scott, "Delta-9-Tetrahydrocannabinol/ cannabidiol (Sativex): A review of its Use in patients with moderate to severe spasticity due to multiple sclerosis," Drugs, vol. 74, no. 5, pp. 563-578, 2014.
10. T. W. Klein, "Cannabinoid-based drugs as anti-inflammatory therapeutics," Nature Reviews Immunology, vol. 5, no. 5, pp. 400-411, 2005.
11. T. W. Klein, C. Newton, K. Larsen et al., "The cannabinoid system and immune modulation," Journal of Leukocyte Biology, vol. 74, no. 4, pp. 486-496, 2003.
12. G. A. Cabral and F. Marciano-Cabral, "Cannabinoid receptors in microglia of the central nervous system: immune functional relevance," Journal of Leukocyte Biology, vol. 78, no. 6, pp. 1192-1197, 2005.
13. D. P. Tashkin, G. C. Baldwin, T. Sarafian, S. Dubinett, and M. D. Roth, "Respiratory and immunologic consequences of marijuana smoking," Journal of Clinical Pharmacology, vol. 42, supplement 11, pp. 71S-81S, 2002.
14. M. D. Roth, G. C. Baldwin, and D. P. Tashkin, "Effects of delta-9-tetrahydrocannabinol on human immune function and host defense," Chemistry and Physics of Lipids, vol. 121, no. 1-2, pp. 229-239, 2002.
15. N. E. Buckley, "The peripheral cannabinoid receptor knockout mice: an update," British Journal of Pharmacology, vol. 153, no. 2, pp. 309-318, 2008.
16. G. C. Baldwin, D. P. Tashkin, D. M. Buckley, A. N. Park, S. M. Dubinett, and M. D. Roth, "Marijuana and cocaine impair alveolar macrophage function and cytokine production," American Journal of Respiratory and Critical CareMedicine, vol. 156, no. 5, pp. 1606-1613, 1997.
17. R. Pacifici, P. Zuccaro, S. Pichini et al., "Modulation of the immune system in cannabis users," The Journal of the American Medical Association, vol. 289, no. 15, pp. 1929-1931, 2003.
18. K. L. McCoy, D. Gainey, and G. A. Cabral, "9-Tetrahydrocannabinolmodulates antigen processing by macrophages," Journal of Pharmacology and ExperimentalTherapeutics, vol. 273, no. 3, pp. 1216-1223, 1995.
19. D. J. Clements, G. A. Cabral, and K. L. McCoy, "9-Tetrahydrocannabinol selectively inhibits macrophage costimulatory activity and down-regulates heat-stable antigen expression," Journal of Pharmacology and Experimental Therapeutics, vol. 277, no. 3, pp. 1315-1321, 1996.
20. K. L. McCoy, M. Matveyeva, S. J. Carlisle, and G. A. Cabral, "Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation," Journal of Pharmacology and ExperimentalTherapeutics, vol. 289, no. 3, pp. 1620-1625, 1999.
21. N. E. Buckley, K. L. McCoy, E. Mezey et al., "Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor," European Journal of Pharmacology, vol. 396, no. 2-3, pp. 141-149, 2000.
22. S. Chuchawankul, M. Shima, N. E. Buckley, C. B. Hartmann, and K. L. McCoy, "Role of cannabinoid receptors in inhibiting macrophage costimulatory activity," International Immunopharmacology, vol. 4, no. 2, pp. 265-278, 2004.
23. J. Liu, S. Bátkai, P. Pacher et al., "Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/ phosphoinositide 3-kinase/NF-κB independently of plateletactivating factor," The Journal of Biological Chemistry, vol. 278, no. 45, pp. 45034-45039, 2003.
24. R. G. Pertwee, A. C. Howlett, M. E. Abood et al., "International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: Beyond CB1 and CB2," Pharmacological Reviews, vol. 62, no. 4, pp. 588-631, 2010.
25. R. G. Pertwee, "Endocannabinoids and their pharmacological actions," Handbook of Experimental Pharmacology, vol. 231, pp. 1-37, 2015.
26. A. J. Hill, C. M. Williams, B. J. Whalley, andG. J. Stephens, "Phytocannabinoids as novel therapeutic agents in CNS disorders," Pharmacology &Therapeutics, vol. 133, no. 1, pp. 79-97, 2012.
27. L. A. Matsuda, S. J. Lolait,M. J. Brownstein, A. C. Young, and T. I. Bonner, "Structure of a cannabinoid receptor and functional expression of the cloned cDNA," Nature, vol. 346, no. 6284, pp. 561-564, 1990.
28. B. F. Thomas, X. Wei, and B. R. Martin, "Characterization and autoradiographic localization of the cannabinoid binding site in rat brain using [3H]11-OH-9-THC-DMH," Journal of Pharmacology and ExperimentalTherapeutics, vol. 263, no. 3,pp. 1383-1390, 1992.
29. S. Munro, K. L. Thomas, and M. Abu-Shaar, "Molecular characterization of a peripheral receptor for cannabinoids," Nature, vol. 365, no. 6441, pp. 61-65, 1993.
30. M. Bouaboula, M. Rinaldi, P. Carayon et al., "Cannabinoidreceptor expression in human leukocytes," European Journal of Biochemistry, vol. 214, no. 1, pp. 173-180, 1993.
31. S. Galiègue, S. Mary, J. Marchand et al., "Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations," European Journal of Biochemistry, vol. 232, no. 1, pp. 54-61, 1995.
32. M. D. Van Sickle, M. Duncan, P. J. Kingsley et al., "Identification and functional characterization of brainstem cannabinoid CB2 receptors," Science, vol. 310, no. 5746, pp. 329-332, 2005.
33. Y. Yiangou, P. Facer, P. Durrenberger et al., "COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages ofmultiple sclerosis and amyotrophic lateral sclerosis spinal cord," BMC Neurology, vol. 6, article 12, 2006.
34. C. Benito, E. Núñez, R. M. Tolón et al., "Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer's disease brains," The Journal of Neuroscience, vol. 23, no. 35, pp. 11136-11141, 2003.
35. P. Valk, S. Verbakel, Y. Vankan et al., "Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells," Blood, vol. 90, no. 4, pp. 1448-1457, 1997.
36. S. N. Noe, C. Newton, R. Widen, H. Friedman, and T. W. Klein, "Anti-CD40, anti-CD3, and IL-2 stimulation induce contrasting changes in CB1 mRNA expression in mouse splenocytes," Journal of Neuroimmunology, vol. 110, no. 1-2, pp. 161-167, 2000.
37. M. Svensson, P. Chen, and O. Hammarfjord, "Dendritic cell regulation by cannabinoid-based drugs," Pharmaceuticals, vol. 3, no. 8, pp. 2733-2750, 2010.
38. T. P. Malan Jr., M. M. Ibrahim, J. Lai, T. W. Vanderah, A. Makriyannis, and F. Porreca, "CB2 cannabinoid receptor agonists: pain relief without psychoactive effects" Current Opinion in Pharmacology, vol. 3, no. 1, pp. 62-67, 2003.
39. S. G. Kinsey, A. Mahadevan, B. Zhao et al., "The CB2 cannabinoid receptor-selective agonist O-3223 reduces pain and inflammation without apparent cannabinoid behavioral effects," Neuropharmacology, vol. 60, no. 2-3, pp. 244-251, 2011.
40. A. C. Howlett, "Cannabinoid receptor signaling," Handbook of Experimental Pharmacology, vol. 168, pp. 53-79, 2005.
41. D. G. Demuth and A. Molleman, "Cannabinoid signalling," Life Sciences, vol. 78, no. 6, pp. 549-563, 2006.
42. M. R. Bell, T. E. D'Ambra, V. Kumar et al., "Antinociceptive (aminoalkyl)indoles," Journal of Medicinal Chemistry, vol. 34, no. 3, pp. 1099-1110, 1991.
43. W. A. Devane, L. Hanus, A. Breuer et al., "Isolationandstructure of a brain constituent that binds to the cannabinoid receptor," Science, vol. 258, no. 5090, pp. 1946-1949, 1992.
44. R. Mechoulam, S. Ben-Shabat, L. Hanus et al., "Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors," Biochemical Pharmacology, vol. 50, no. 1, pp. 83-90, 1995.
45. T. Sugiura, S. Kondo, A. Sukagawa et al., "2-arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain," Biochemical and Biophysical Research Communications, vol. 215, no. 1, pp. 89-97, 1995.
46. V. Di Marzo, "2-Arachidonoyl-glycerol as an 'endocannabinoid': limelight for a formerly neglected metabolite," Biochemistry, vol. 63, no. 1, pp. 13-21, 1998.
47. A. C. Howlett and R. M. Fleming, "Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membrane," Molecular Pharmacology, vol. 26, no. 3, pp. 532-538, 1984.
48. A. C. Howlett, J. M. Qualy, and L. L. Khachatrian, "Involvement of G(i) in the inhibition of adenylate cyclase by cannabimimetic drugs,"Molecular Pharmacology, vol. 29,no. 3, pp. 307-313, 1986.
49. V. Rubovitch, M. Gafni, and Y. Sarne, "The involvement of VEGF receptors andMAPK in the cannabinoid potentiation of Ca2+ flux into N18TG2 neuroblastoma cells," Molecular Brain Research, vol. 120, no. 2, pp. 138-144, 2004.
50. M. Bouaboula, C. Poinot-Chazel, B. Bourrie et al., "Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1," Biochemical Journal, vol. 312, no. 2, pp. 637-641, 1995.
51. E. J. Carrier, C. S. Kearn, A. J. Barkmeier et al., "Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependentmechanism,"Molecular Pharmacology, vol. 65, no. 4, pp. 999-1007, 2004.
52. B. L. Faubert Kaplan andN. E. Kaminski, "Cannabinoids inhibit the activation of ERK MAPK in PMA/Io-stimulated mouse splenocytes," International Immunopharmacology, vol. 3, no. 10-11, pp. 1503-1510, 2003.
53. O. Gomez, M. A. Sanchez-Rodriguez, S. Ortega-Gutierrez et al., "A basal tone of 2-arachidonoylglycerol contributes to early oligodendrocyte progenitor proliferation by activating phosphatidylinositol 3-kinase (PI3K)/AKT and theMammalian Target of Rapamycin (MTOR) pathways," Journal of Neuroimmune Pharmacology, vol. 10, no. 2, pp. 309-317, 2015.
54. J. Palazuelos, Z. Ortega, J. Dáz-Alonso, M. Guzmán, and I. Galve-Roperh, "CB2 cannabinoid receptors promote neural progenitor cell proliferation via mTORC1 signaling," The Journal of Biological Chemistry, vol. 287, no. 2, pp. 1198-1209, 2012.
55. C. Morell, A. Bort, D. Vara, A. Ramos-Torres, N. Rodrguez-Henche, and I. Dáz-Laviada, "The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells," Prostate Cancer and Prostatic Diseases, 2016.
56. N. Stella, "Endocannabinoid signaling in microglial cells," Neuropharmacology, vol. 56, no. 1, pp. 244-253, 2009.
57. P. Pacher and G. Kunos, "Modulating the endocannabinoid system in human health and disease: successes and failures," FEBS Journal, vol. 280, no. 9, pp. 1918-1943, 2013.
58. V. Di Marzo, A. Fontana, H. Cadas et al., "Formation and inactivation of endogenous cannabinoid anandamide in central neurons," Nature, vol. 372, no. 6507, pp. 686-691, 1994.
59. J. M. Walker, S. M. Huang, N. M. Strangman, K. Tsou, andM. C. Sañudo-Peña, "Pain modulation by release of the endogenous cannabinoid anandamide," Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 21, pp. 12198-12203, 1999.
60. N. Stella and D. Piomelli, "Receptor-dependent formation of endogenous cannabinoids in cortical neurons," European Journal of Pharmacology, vol. 425, no. 3, pp. 189-196, 2001.
61. F. Béquet, F. Uzabiaga, M. Desbazeille et al., "CB1 receptormediated control of the release of endocannabinoids (as assessed by microdialysis coupled with LC/MS) in the rat hypothalamus," European Journal of Neuroscience, vol. 26, no. 12, pp. 3458-3464, 2007.
62. V. Di Marzo, "Targeting the endocannabinoid system: to enhance or reduce" Nature Reviews Drug Discovery, vol. 7, no. 5, pp. 438-455, 2008.
63. V. Di Marzo, L. De Petrocellis, and T. Bisogno, "The biosynthesis, fate and pharmacological properties of endocannabinoids," in Cannabinoids, vol. 168 of Handbook in Experimental Pharmacology, pp. 147-185, Springer, Berlin, Germany, 2005.
64. R. Pandey, K. Mousawy, M. Nagarkatti, and P. Nagarkatti, "Endocannabinoids and immune regulation," Pharmacological Research, vol. 60, no. 2, pp. 85-92, 2009.
65. M. G. Cascio and P. Marini, "Biosynthesis and fate of endocannabinoids," Handbook of Experimental Pharmacology, vol. 231, pp. 39-58, 2015.
66. B. F. Cravatt, K. Demarest, M. P. Patricelli et al., "Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase," Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 16, pp. 9371-9376, 2001.
67. M. Beltramo and D. Piomelli, "Carrier-mediated transport and enzymatic hydrolysis of the endogenous cannabinoid 2-arachidonylglycerol," NeuroReport, vol. 11, no. 6, pp. 1231-1235, 2000.
68. C. A. Janeway Jr., "Approaching the asymptote? Evolution and revolution in immunology," Cold Spring Harbor Symposia on Quantitative Biology, vol. 54, no. 1, pp. 1-13, 1989.
69. G. Santoni, C. Cardinali, B. Morelli, M. Santoni, M. Nabissi, and C. Amantini, "Danger-and pathogen-associatedmolecular 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," Journal of Neuroinflammation, vol. 12, no. 1, article 21, 10 pages, 2015.
70. S. W. Brubaker, K. S. Bonham, I. Zanoni, and J. C. Kagan, "Innate immune pattern recognition: a cell biological perspective," Annual Review of Immunology, vol. 33, pp. 257-290, 2015.
71. L. A. J. O'Neill, "When signaling pathways collide: positive and negative regulation of Toll-like receptor signal transduction," Immunity, vol. 29, no. 1, pp. 12-20, 2008.
72. B. L. Lee and G. M. Barton, "Trafficking of endosomal Toll-like receptors," Trends in Cell Biology, vol. 24, no. 6, pp. 360-369, 2014.
73. T. Kawasaki and T. Kawai, "Toll-like receptor signaling pathways," Frontiers in Immunology, vol. 5, article 461, 8 pages, 2014.
74. J. C. Kagan, T. Su, T. Horng, A. Chow, S. Akira, and R. Medzhitov, "TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-,"Nature Immunology, vol. 9, no. 4, pp. 361-368, 2008.
75. N. Tanimura, S. Saitoh, F. Matsumoto, S. Akashi-Takamura, and K. Miyake, "Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling," Biochemical and Biophysical Research Communications, vol. 368, no. 1, pp. 94-99, 2008.
76. A. M. Piccinini andK. S. Midwood, "DAMPening inflammation by modulating TLR signalling," Mediators of Inflammation, vol. 2010, Article ID672395, 21 pages, 2010.
77. D. Stein, S. Roth, E. Vogelsang, and C. Nüsslein-Volhard, "The polarity of the dorsoventral axis in the Drosophila embryo is defined by an extracellular signal," Cell, vol. 65, no. 5, pp. 725-735, 1991.
78. C. Hashimoto, K. L. Hudson, and K. V. Anderson, "TheToll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein," Cell, vol. 52, no. 2, pp. 269-279, 1988.
79. B. Lemaitre, E. Nicolas, L. Michaut, J.-M. Reichhart, and J. A. Hoffmann, "The dorsoventral regulatory gene cassette spatzle/Toll/Cactus controls the potent antifungal response in Drosophila adults," Cell, vol. 86, no. 6, pp. 973-983, 1996.
80. N. Nomura, N. Miyajima, T. Sazuka et al., "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1," DNA Research, vol. 1, no. 1, pp. 27-35, 1994.
81. R. Medzhitov, P. Preston-Hurlburt, and C. A. Janeway Jr., "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity," Nature, vol. 388, no. 6640, pp. 394-397, 1997.
82. P. Matzinger, "Essay 1: the danger model in its historical context," Scandinavian Journal of Immunology, vol. 54, no. 1-2, pp. 4-9, 2001.
83. K. Ohashi, V. Burkart, S. Flohé, andH. Kolb, "Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex," The Journal of Immunology, vol. 164, no. 2, pp. 558-561, 2000.
84. S. Basu, R. J. Binder, R. Suto, K. M. Anderson, and P. K. Srivastava, "Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway," International Immunology, vol. 12, no. 11, pp. 1539-1546, 2000.
85. M. Li, D. F. Carpio, Y. Zheng et al., "An essential role of theNF-κB/toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells," The Journal of Immunology, vol. 166, no. 12, pp. 7128-7135, 2001.
86. C. Qian and X. Cao, "Regulation of Toll-like receptor signaling pathways in innate immune responses," Annals of the New York Academy of Sciences, vol. 1283, no. 1, pp. 67-74, 2013.
87. T. L. Gioannini and J. P. Weiss, "Regulation of interactions of Gram-negative bacterial endotoxins with mammalian cells," Immunologic Research, vol. 39, no. 1-3, pp. 249-260, 2007.
88. K. Hoebe, P. Georgel, S. Rutschmann et al., "CD36 is a sensor of diacylglycerides," Nature, vol. 433, no. 7025, pp. 523-527, 2005.
89. R. L. Silverstein and M. Febbraio, "CD36, a scavenger receptor involved in immunity,metabolism, angiogenesis, and behavior," Science Signaling, vol. 2, no. 72, article re3, 16 pages, 2009.
90. R. N. Miguel, J. Wong, J. F. Westoll et al., "A dimer of the toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins," PLoS ONE, vol. 2, no. 8, article e788, 2007.
91. B. Verstak, C. J. Arnot, and N. J. Gay, "An alanine-to-proline mutation in the BB-loop of TLR3 Toll/IL-1R domain switches signalling adaptor specificity fromTRIF toMyD88,"TheJournal of Immunology, vol. 191, no. 12, pp. 6101-6109, 2013.
92. L. Mestre, F. Correa,A. Arévalo-Martín et al., "Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis," Journal of Neurochemistry, vol. 92, no. 6, pp. 1327-1339, 2005.
93. Y.-H. Chang, S. T. Lee, and W.-W. Lin, "Effects of cannabinoids on LPS-stimulated inflammatory mediator release from macrophages: involvement of eicosanoids," Journal of Cellular Biochemistry, vol. 81, no. 4, pp. 715-723, 2001.
94. W. Zhu, C. Newton, Y. Daaka, H. Friedman, and T. W. Klein, "9-tetrahydrocannabinol enhances the secretion of interleukin 1 fromendotoxin-stimulated macrophages," Journal of Pharmacology and ExperimentalTherapeutics, vol. 270, no. 3, pp. 1334-1339, 1994.
95. R. B. Zurier, R. G. Rossetti, S. H. Burstein, and B. Bidinger, "Suppression of human monocyte interleukin-1 production by ajulemic acid, a nonpsychoactive cannabinoid," Biochemical Pharmacology, vol. 65, no. 4, pp. 649-655, 2003.
96. B. Watzl, P. Scuderi, and R. R. Watson, "Marijuana components stimulate human peripheral blood mononuclear cell secretion of interferon- and suppress interleukin-1 in vitro," International Journal of Immunopharmacology, vol. 13, no. 8, pp. 1091-1097, 1991.
97. E. V. Berdyshev, E. Boichot, N. Germain, N. Allain, J.-P. Anger, and V. Lagente, "Influence of fatty acid ethanolamides and9-tetrahydrocannabinol on cytokine and arachidonate release by mononuclear cells," European Journal of Pharmacology, vol. 330, no. 2-3, pp. 231-240, 1997.
98. L. Nong, C. Newton, Q. Cheng, H. Friedman, M. D. Roth, and T. W. Klein, "Altered cannabinoid receptormRNA expression in peripheral blood mononuclear cells from marijuana smokers," Journal of Neuroimmunology, vol. 127, no. 1-2, pp. 169-176, 2002.
99. Z.-M. Zheng and S. C. Specter, "Delta-9-tetrahydrocannabinol suppresses tumor necrosis factor maturation and secretion but not its transcription in mouse macrophages," International Journal of Immunopharmacology, vol. 18, no. 1, pp. 53-68, 1996.
100. K. Fischer-Stenger, D. A. D. Pettit, and G. A. Cabral, "9-tetrahydrocannabinol inhibition of tumor necrosis factor-: suppression of post-translational events," Journal of Pharmacology and ExperimentalTherapeutics, vol. 267, no. 3, pp. 1558-1565, 1993.
101. S. V. More, J.-Y. Park, B.-W. Kim et al., "Anti-neuroinflammatory activity of a novel cannabinoid derivative by inhibiting the NF-κB signaling pathway in lipopolysaccharide-induced BV-2 microglial cells," Journal of Pharmacological Sciences, vol. 121, no. 2, pp. 119-130, 2013.
102. R. G. Coffey, Y. Yamamoto, E. Snella, and S. Pross, "Tetrahydrocannabinol inhibition of macrophage nitric oxide production," Biochemical Pharmacology, vol. 52, no. 5, pp. 743-751, 1996.
103. R. A. Puffenbarger, A. C. Boothe, and G. A. Cabral, "Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells," Glia, vol. 29, no. 1, pp. 58-69, 2000.
104. Y. L. Jeon, K. H. Yang, J. T. Pulaski, andN. E. Kaminski, "Attenuation of inducible nitric oxide synthase gene expression by delta 9-tetrahydrocannabinol is mediated through the inhibition of nuclear factor-κB/Rel activation,"Molecular Pharmacology, vol. 50, no. 2, pp. 334-341, 1996.
105. R. Echigo, N. Sugimoto, A. Yachie, and T. Ohno-Shosaku, "Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells," Oncology Reports, vol. 28, no. 4, pp. 1176-1180, 2012.
106. H. Xu, C. L. Cheng, M. Chen et al., "Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH-133 in a rodent model of autoimmune uveoretinitis," Journal of Leukocyte Biology, vol. 82, no. 3, pp. 532-541, 2007.
107. M. Guzmán, "Effects on cell viability," Handbook of Experimental Pharmacology, vol. 168, pp. 627-642, 2005.
108. S. A. Rieder, A. Chauhan, U. Singh, M. Nagarkatti, and P. Nagarkatti, "Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression," Immunobiology, vol. 215, no. 8, pp. 598-605, 2010.
109. F. Correa, L. Mestre, F. Docagne, and C. Guaza, "Activation of cannabinoid CB2 receptor negatively regulates IL-12p40 production in murine macrophages: role of IL-10 and ERK1/2 kinase signaling," British Journal of Pharmacology, vol. 145, no. 4, pp. 441-448, 2005.
110. F. Correa, M. Hernangómez, L. Mestre et al., "Anandamide enhances IL-10 production in activated microglia by targeting CB2 receptors: roles of ERK1/2, JNK, andNF-κB," Glia, vol. 58, no. 2, pp. 135-147, 2010.
111. F. Molina-Holgado, E. Pinteaux, J. D. Moore et al., "Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia," Journal of Neuroscience, vol. 23, no. 16, pp. 6470-6474, 2003.
112. M. Roche, M. Diamond, J. P. Kelly, and D. P. Finn, "In vivo modulation of LPS-induced alterations in brain and peripheral cytokines and HPA axis activity by cannabinoids," Journal of Neuroimmunology, vol. 181, no. 1-2, pp. 57-67, 2006.
113. E. Berdyshev, E. Boichot, M. Corbel, N. Germain, and V. Lagente, "Effects of cannabinoid receptor ligands on LPSinduced pulmonary inflammation in mice," Life Sciences, vol. 63, no. 8, pp. 125-129, 1998.
114. S. R. Smith, C. Terminelli, and G. Denhardt, "Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice," Journal of Pharmacology and ExperimentalTherapeutics, vol. 293, no. 1, pp. 136-150, 2000.
115. R. Gallily, A. Yamin, Y. Waksmann et al., "Protection against septic shock and suppression of tumor necrosis factor and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid," Journal of Pharmacology and Experimental Therapeutics, vol. 283, no. 2, pp. 918-924, 1997.
116. S. Tomar, E. E. Zumbrun, M. Nagarkatti, and P. S. Nagarkatti, "Protective role of cannabinoid receptor 2 activation in galactosamine/lipopolysaccharide-induced acute liver failure through regulation of macrophage polarization and MicroRNAs," Journal of Pharmacology and Experimental Therapeutics, vol. 353, no. 2, pp. 369-379, 2015.
117. A. M. Malfitano, S. Basu, K. Maresz, M. Bifulco, and B. N. Dittel, "What we know and do not know about the cannabinoid receptor 2 (CB2)," Seminars in Immunology, vol. 26, no. 5, pp. 369-379, 2014.
118. J. Tschöp, K. R. Kasten, R. Nogueiras et al., "The cannabinoid receptor 2 is critical for the host response to sepsis," The Journal of Immunology, vol. 183, no. 1, pp. 499-505, 2009.
119. M. Karsak, E. Gaffal, R. Date et al., "Attenuation of allergic contact dermatitis through the endocannabinoid system," Science, vol. 316, no. 5830, pp. 1494-1497, 2007.
120. J. P. Buchweitz, P. W. F. Karmaus, K. J. Williams, J. R. Harkema, and N. E. Kaminski, "Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of9-tetrahydrocannabinol," Journal of Leukocyte Biology, vol. 83, no. 3, pp. 785-796, 2008.
121. P. W. F. Karmaus, W. Chen, R. Crawford, B. L. F. Kaplan, and N. E. Kaminski, "9-Tetrahydrocannabinol impairs the inflammatory response to influenza infection: role of antigenpresenting cells and the cannabinoid receptors 1 and 2," Toxicological Sciences, vol. 131, no. 2, pp. 419-433, 2013.
122. M. D. Roth, J. T. Castaneda, and S. M. Kiertscher, "Exposure to9-tetrahydrocannabinol impairs the differentiation of human monocyte-derived dendritic cells and their capacity for T cell activation," Journal of Neuroimmune Pharmacology, vol. 10, no. 2, pp. 333-343, 2015.
123. S. Merighi, S. Gessi, K. Varani et al., "Cannabinoid CB2 receptors modulate ERK-1/2 kinase signalling and NO release in microglial cells stimulated with bacterial lipopolysaccharide," British Journal of Pharmacology, vol. 165, no. 6, pp. 1773-1788, 2012.
124. Y. Waksman, J. M. Olson, S. J. Carlisle, and G. A. Cabral, "The central cannabinoid receptor CB1 mediates inhibition of nitric oxide production by rat microglial cells," Journal of Pharmacology and Experimental Therapeutics, vol. 288, no. 3, pp. 1357-1366, 1999.
125. E. Kozela, M. Pietr, A. Juknat, N. Rimmerman, R. Levy, and Z. Vogel, "Cannabinoids9-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-κB and interferon-/STAT proinflammatory pathways in BV-2 microglial cells," The Journal of Biological Chemistry, vol. 285, no. 3, pp. 1616-1626, 2010.
126. E. J. Downer, E. Clifford, B. Gran, H. J. Nel, P. G. Fallon, and P. N. Moynagh, "Identification of the synthetic cannabinoid R(+)WIN55,212-2 as a novel regulator of IFN regulatory factor 3 activation and IFN- expression: relevance to therapeutic effects in models of multiple sclerosis," Journal of Biological Chemistry, vol. 286, no. 12, pp. 10316-10328, 2011.
127. E. J. Downer, E. Clifford, S. Amu, P. G. Fallon, and P. N. Moynagh, "The synthetic cannabinoid R(+)WIN55,212-2 augments interferon- expression via peroxisome proliferator-activated receptor-," Journal of Biological Chemistry, vol. 287, no. 30, pp. 25440-25453, 2012.
128. S. J. Carlisle, F. Marciano-Cabral, A. Staab, C. Ludwick, and G. A. Cabral, "Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation," International Immunopharmacology, vol. 2, no. 1, pp. 69-82, 2002.
129. L. Walter, A. Franklin, A. Witting et al., "Nonpsychotropic cannabinoid receptors regulate microglial cell migration," The Journal of Neuroscience, vol. 23, no. 4, pp. 1398-1405, 2003.
130. K. Maresz, E. J. Carrier, E. D. Ponomarev, C. J. Hillard, and B. N. Dittel, "Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli," Journal of Neurochemistry, vol. 95, no. 2, pp. 437-445, 2005.
131. G. A. Cabral, E. S. Raborn, L. Griffin, J. Dennis, and F. Marciano-Cabral, "CB2 receptors in the brain: role in central immune function," British Journal of Pharmacology, vol. 153, no. 2, pp. 240-251, 2008.
132. S. Mukhopadhyay, S. Das, E. A. Williams et al., "Lipopolysaccharide and cyclicAMP regulation of CB2 cannabinoid receptor levels in rat brain andmouse RAW264. 7 macrophages," Journal of Neuroimmunology, vol. 181, no. 1-2, pp. 82-92, 2006.
133. R. M. Concannon, B. N. Okine, D. P. Finn, and E. Dowd, "Differential upregulation of the cannabinoid CB2 receptor in neurotoxic and inflammation-driven rat models of Parkinson's disease," Experimental Neurology, vol. 269, pp. 133-141, 2015.
134. M. L. Wolfson, J. Aisemberg, A. I. Salazar, A. P. Domnguez Rubio, C. A. Vercelli, and A. M. Franchi, "Progesterone reverts LPS-reduced FAAH activity inmurine peripheral blood mononuclear cells by a receptor-mediated fashion," Molecular and Cellular Endocrinology, vol. 381, no. 1-2, pp. 97-105, 2013.
135. B. Szafran, A. Borazjani, J. H. Lee, M. K. Ross, and B. L. F. Kaplan, "Lipopolysaccharide suppresses carboxylesterase 2G activity and 2-arachidonoylglycerol hydrolysis: a possible mechanism to regulate inflammation," Prostaglandins and Other Lipid Mediators, vol. 121, pp. 199-206, 2015.
136. K. Varga, J. A. Wagner, D. T. Bridgen, and G. Kunos, "Platelet-and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension," FASEB Journal, vol. 12, no. 11, pp. 1035-1044, 1998.
137. V. K. Pestonjamasp and S. H. Burstein, "Anandamide synthesis is induced by arachidonate mobilizing agonists in cells of the immune system," Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism, vol. 1394, no. 2-3, pp. 249-260, 1998.
138. I. Matias, P. Pochard, P. Orlando, M. Salzet, J. Pestel, and V. Di Marzo, "Presence and regulation of the endocannabinoid systeminhumandendritic cells," European Journal of Biochemistry, vol. 269, no. 15, pp. 3771-3778, 2002.
139. H. Friedman, T. W. Klein,C. Newton, andY. Daaka, "Marijuana, receptors and immunomodulation," Advances in Experimental Medicine and Biology, vol. 373, pp. 103-113, 1995.
140. V. Di Marzo, T. Bisogno, L. De Petrocellis et al., "Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages," European Journal of Biochemistry, vol. 264, no. 1, pp. 258-267, 1999.
141. C. J. Hillard, R. A. Harris, and A. S. Bloom, "Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: fluorescence studies," Journal of Pharmacology and Experimental Therapeutics, vol. 232, no. 3, pp. 579-588, 1985.
142. http://www. fda. gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/ approvalapplications/therapeuticbiologicapplications/ ucm080402. htm.
143. K. H. Han, S. Lim, J. Ryu et al., "CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages," Cardiovascular Research, vol. 84, no. 3, pp. 378-386, 2009.
144. Y. Daaka, T. W. Klein, and H. Friedman, "Expression of cannabinoid receptormRNAinmurine and human leukocytes," Advances in ExperimentalMedicine and Biology, vol. 373, pp. 91-96, 1995.
145. S. Kishimoto, M. Gokoh, S. Oka et al., "2-arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoidCB2 receptor-dependentmechanism," Journal of Biological Chemistry, vol. 278, no. 27, pp. 24469-24475, 2003.
146. A. Klegeris, C. J. Bissonnette, and P. L. McGeer, "Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor," British Journal of Pharmacology, vol. 139, no. 4, pp. 775-786, 2003.
147. J. Parker, F. Atez, R. G. Rossetti, A. Skulas, R. Patel, and R. B. Zurier, "Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid," Rheumatology International, vol. 28, no. 7, pp. 631-635, 2008.
148. D. Avni, O. Ernst, A. Philosoph, and T. Zor, "Role of CREB in modulation of TNF and IL-10 expression in LPS-stimulated RAW264. 7 macrophages," Molecular Immunology, vol. 47, no. 7-8, pp. 1396-1403, 2010.
149. M. Maccarrone, M. Bari, N. Battista, and A. Finazzi-Agrò, "Endocannabinoid degradation, endotoxic shock and inflammation," Current Drug Targets-Inflammation and Allergy, vol. 1, no. 1, pp. 53-63, 2002.
150. N. Stella, "Cannabinoid signaling in glial cells," Glia, vol. 48, no. 4, pp. 267-277, 2004.