Cannabinoid receptor-mediated regulation of intracellular calcium by Δ9-tetrahydrocannabinol in resting T cells
Tóm tắt
Cannabinoids exhibit broad immune modulating activity by targeting many cell types within the immune system, including T cells, which exhibit sensitivity, as evidenced by altered activation, proliferation, and cytokine expression. As a result of the critical role calcium plays in T cell function coupled with previous findings demonstrating disruption of the calcium-regulated transcription factor, nuclear factor of activated T cells, by cannabinoid treatment the objective of the present investigation was to perform an initial characterization of the role of the cannabinoid receptors in the regulation of the intracellular calcium concentration ([Ca2+]i) by Δ9-tetrahydrocannabinol (Δ9-THC) in T lymphocytes. Here, we demonstrate that Δ9-THC robustly elevates [Ca2+]i in purified murine splenic T cells and in the human peripheral blood acute lymphoid leukemia (HPB-ALL) human T cell line but only minimally elevates [Ca2+]i in Jurkat E6-1 (dysfunctional cannabinoid receptor 2-expressing) human T cells. Removal of extracellular calcium severely attenuated the Δ9-THC-mediated rise in [Ca2+]i in murine splenic T cells and HPB-ALL cells. Pretreatment with cannabinoid receptor antagonists, SR144528 and/or SR141716A, led to an attenuation of Δ9-THC-mediated elevation in [Ca2+]i in splenic T cells and HPB-ALL cells but not in Jurkat E6-1 cells. Furthermore, pretreatment of HPB-ALL cells with SR144528 antagonized the small rise in [Ca2+]i elicited by Δ9-THC in the absence of extracellular calcium. These findings suggest that Δ9-THC induces an influx of extracellular calcium in resting T cells in a cannabinoid receptor-dependent manner.
Từ khóa
Tài liệu tham khảo
Klein, 1998, Cannabinoid receptors and immunity, Immunol. Today, 19, 373, 10.1016/S0167-5699(98)01300-0
Schatz, 1993, Δ9-Tetrahydrocanabinol selectively inhibits T-cell-dependent humoral immune responses through direct inhibition of accessory T-cell function, Immunopharmacology, 26, 129, 10.1016/0162-3109(93)90005-B
Condie, 1996, Cannabinoid inhibition of adenylate cyclase-mediated signal transduction and interleukin 2 (IL-2) expression in the murine T-cell line, EL4.IL-2, J. Biol. Chem., 271, 13175, 10.1074/jbc.271.22.13175
Newton, 1998, The role of macrophages in THC-induced alteration of the cytokine network, Adv. Exp. Med. Biol., 437, 207, 10.1007/978-1-4615-5347-2_23
Klein, 2000, The cannabinoid system and cytokine network, Proc. Soc. Exp. Biol. Med., 225, 1, 10.1046/j.1525-1373.2000.22501.x
Jan, 2002, Cannabinol enhancement of interleukin-2 (IL-2) expression by T cells is associated with an increase in IL-2 distal nuclear factor of activated T cell activity, Mol. Pharmacol., 61, 446, 10.1124/mol.61.2.446
Ouyang, 1998, Suppression of interleukin-2 by the putative endogenous cannabinoid 2-arachidonyl-glycerol is mediated through down-regulation of the nuclear factor of activated T cells, Mol. Pharmacol., 53, 676, 10.1124/mol.53.4.676
Yea, 2000, Role of nuclear factor of activated T-cells and activator protein-1 in the inhibition of interleukin-2 gene transcription by cannabinol in EL4 T-cells, J. Pharmacol. Exp. Ther., 292, 597
Rao, 1997, Transcription factors of the NFAT family: regulation and function, Annu. Rev. Immunol., 15, 707, 10.1146/annurev.immunol.15.1.707
Lewis, 2001, Calcium signaling mechanisms in T lymphocytes, Annu. Rev. Immunol., 19, 497, 10.1146/annurev.immunol.19.1.497
Nghiem, 1994, Interleukin-2 transcriptional block by multifunctional Ca2+/calmodulin kinase, Nature, 371, 347, 10.1038/371347a0
Nakayama, 1992, In vivo calcium elevations in thymocytes with T cell receptors that are specific for self ligands, Science, 257, 96, 10.1126/science.1621102
Schwartz, 1992, Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy, Cell, 71, 1065, 10.1016/S0092-8674(05)80055-8
Harding, 1992, CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones, Nature, 356, 607, 10.1038/356607a0
Faubert Kaplan, 2003, Evidence for cannabinoid receptor-dependent and -independent mechanisms of action in leukocytes, J. Pharmacol. Exp. Ther., 306, 1077, 10.1124/jpet.103.051961
Matsuda, 1990, Structure of a cannabinoid receptor and functional expression of the cloned cDNA, Nature, 346, 561, 10.1038/346561a0
Munro, 1993, Molecular characterization of peripheral receptor for cannabinoids, Nature, 365, 61, 10.1038/365061a0
Shire, 1996, Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor, Biochim. Biophys. Acta, 1307, 132, 10.1016/0167-4781(96)00047-4
Berdyshev, 2000, Cannabinoid receptors and the regulation of immune response, Chem. Phys. Lipids, 108, 169, 10.1016/S0009-3084(00)00195-X
Bouaboula, 1993, Cannabinoid-receptor expression in human leukocytes, Eur. J. Biochem., 214, 173, 10.1111/j.1432-1033.1993.tb17910.x
Schatz, 1997, Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system, Toxicol. Appl. Pharmacol., 142, 278, 10.1006/taap.1996.8034
Yebra, 1992, Δ9-Tetrahydrocannabinol suppresses concanavalin A-induced increase in cytoplasmic-free calcium in mouse thymocytes, Life Sci., 51, 151, 10.1016/0024-3205(92)90009-E
Putney, 2001, Mechanisms of capacitative calcium entry, J. Cell Sci., 114, 2223, 10.1242/jcs.114.12.2223
Glass, 1999, Agonist selective regulation of G proteins by cannabinoid CB(1) and CB(2) receptors, Mol. Pharmacol., 56, 1362, 10.1124/mol.56.6.1362
Bouaboula, 1999, Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2: implication for intracellular signalization cross-regulation, Mol. Pharmacol., 55, 473
Casanova, 2003, Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors, J. Clin. Invest., 111, 43, 10.1172/JCI200316116
Calandra, 1999, Dual intracellular signaling pathways mediated by the human cannabinoid CB1 receptor, Eur. J. Pharmacol., 374, 445, 10.1016/S0014-2999(99)00349-0
Glass, 1997, Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor, J. Neurosci., 17, 5327, 10.1523/JNEUROSCI.17-14-05327.1997
Mukhopadhyay, 2001, CB1 receptor-G protein association. Subtype selectivity is determined by distinct intracellular domains, Eur. J. Biochem., 268, 499, 10.1046/j.1432-1327.2001.01810.x
Mukhopadhyay, 2002, CB(1) cannabinoid receptor-G protein association: a possible mechanism for differential signaling, Chem. Phys. Lipids, 121, 91, 10.1016/S0009-3084(02)00153-6
Rinaldi-Carmona, 1994, SR141716A, a potent and selective antagonist of the brain cannabinoid receptor, FEBS Lett., 350, 240, 10.1016/0014-5793(94)00773-X
Showalter, 1996, Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands, J. Pharmacol. Exp. Ther., 278, 989