Δ9-Tetrahydrocannabinol làm giảm phản ứng của cơ thể chủ với ối ghép đồng loại và trì hoãn sự từ chối của ối ghép da thông qua việc kích hoạt thụ thể cannabinoid 1 và sự induction của các tế bào ức chế có nguồn gốc tủy
Tóm tắt
Các tế bào miễn dịch đã được chứng minh là thể hiện các thụ thể cannabinoid và sản xuất các ligand nội sinh. Hơn nữa, việc kích hoạt các thụ thể cannabinoid trên các tế bào miễn dịch đã được chứng minh là kích hoạt sự ức chế miễn dịch mạnh mẽ. Mặc dù có những nghiên cứu như vậy, vai trò của cannabinoids trong cấy ghép, đặc biệt là để ngăn ngừa sự từ chối của ối ghép đồng loại, chưa, theo hiểu biết của chúng tôi, được điều tra trước đây. Trong nghiên cứu hiện tại, chúng tôi đã thử nghiệm tác động của THC lên sự ức chế HvGD cũng như sự từ chối của ối ghép da đồng loại. Để thực hiện điều này, chúng tôi đã nghiên cứu HvGD bằng cách tiêm tế bào lách H-2k vào chuột H-2b và phân tích phản ứng miễn dịch trong các hạch bạch huyết thoát lưu. Điều trị bằng THC đã giảm đáng kể sự phát triển và kích hoạt tế bào T trong các hạch bạch huyết thoát lưu của chuột nhận và giảm các cytokine chỉ dấu sự từ chối ở giai đoạn đầu, bao gồm IL-2 và IFN-γ. Điều trị bằng THC cũng gia tăng sự sống sót của ối ghép da đồng loại. Điều trị bằng THC ở chuột HvGD dẫn đến sự xuất hiện của các MDSC. Sử dụng các nghiên cứu làm sạch MDSC cũng như các thí nghiệm truyền tế bào, chúng tôi đã nhận thấy rằng MDSC được kích hoạt bởi THC là cần thiết cho việc giảm mạnh HvGD. Thêm vào đó, bằng cách sử dụng các chất ức chế dược lý của các thụ thể CB1 và CB2 cùng với các chuột knockout CB1 và CB2, chúng tôi đã thấy rằng THC hoạt động chủ yếu thông qua CB1. Tóm lại, nghiên cứu của chúng tôi cho thấy, lần đầu tiên theo hiểu biết của chúng tôi, rằng việc nhắm đến các thụ thể cannabinoid có thể cung cấp một phương pháp điều trị mới nhằm giảm HvGD và ngăn ngừa sự từ chối của ối ghép.
Từ khóa
#cannabinoids #tế bào miễn dịch #ối ghép đồng loại #THC #thụ thể cannabinoid 1 #tế bào ức chế có nguồn gốc tủyTài liệu tham khảo
Powell, 1999, The -180 site of the IL-2 promoter is the target of CREB/CREM binding in T cell anergy, J. Immunol., 163, 6631, 10.4049/jimmunol.163.12.6631
Campara, 2010, Interleukin-2 receptor blockade with humanized monoclonal antibody for solid organ transplantation, Expert Opin. Biol. Ther., 10, 959, 10.1517/14712598.2010.485187
Villarroel, 2009, Mycophenolate mofetil: an update, Drugs Today (Barc.), 45, 521, 10.1358/dot.2009.45.7.1384878
Grenda, 2010, Steroid minimization in pediatric renal transplantation: early withdrawal or avoidance?, Pediatr. Transplant., 14, 961, 10.1111/j.1399-3046.2010.01403.x
Van den Hof, 2014, Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity, Toxicology, 324, 18, 10.1016/j.tox.2014.06.003
Engels, 2011, Spectrum of cancer risk among US solid organ transplant recipients, JAMA, 306, 1891, 10.1001/jama.2011.1592
Ghaziani, 2014, Hepatitis B and liver transplantation: molecular and clinical features that influence recurrence and outcome, World, J. Gastroenterol., 20, 14142, 10.3748/wjg.v20.i39.14142
Gaoni, 1964, Isolation, structure, and partial synthesis of an active constituent of hashish, J. Am. Chem. Soc., 86, 1646, 10.1021/ja01062a046
Munro, 1993, Molecular characterization of a peripheral receptor for cannabinoids, Nature, 365, 61, 10.1038/365061a0
Matsuda, 1990, Structure of a cannabinoid receptor and functional expression of the cloned cDNA, Nature, 346, 561, 10.1038/346561a0
Tanasescu, 2010, Cannabinoids and the immune system: an overview, Immunobiology, 215, 588, 10.1016/j.imbio.2009.12.005
Moldrich, 2000, Localization of the CB1 cannabinoid receptor in the rat brain: an immunohistochemical study, Peptides, 21, 1735, 10.1016/S0196-9781(00)00324-7
Parolaro, 1999, Presence and functional regulation of cannabinoid receptors in immune cells, Life Sci., 65, 637, 10.1016/S0024-3205(99)00286-6
Onaivi, 2006, Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain, Ann. N. Y. Acad. Sci., 1074, 514, 10.1196/annals.1369.052
Glass, 1999, Agonist selective regulation of G proteins by cannabinoid CB1 and CB2 receptors, Mol. Pharmacol., 56, 1362, 10.1124/mol.56.6.1362
Felder, 1995, Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors, Mol. Pharmacol., 48, 443
Agudelo, 2008, Cannabinoid receptor 2 (CB2) mediates immunoglobulin class switching from IgM to IgE in cultures of murine-purified B lymphocytes, J. Neuroimmune Pharmacol., 3, 35, 10.1007/s11481-007-9088-9
Newton, 2009, CB1 and CB2 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., 4, 92, 10.1007/s11481-008-9126-2
Börner, 2007, Activation of human T cells induces upregulation of cannabinoid receptor type 1 transcription, Neuroimmunomodulation, 14, 281, 10.1159/000117809
Nagarkatti, 2009, Cannabinoids as novel anti-inflammatory drugs, Future medicinal chemistry, 1, 1333, 10.4155/fmc.09.93
Klein, 2003, The cannabinoid system and immune modulation, J. Leukoc. Biol., 74, 486, 10.1189/jlb.0303101
Grotenhermen, 2004, Pharmacology of cannabinoids, Neuroendocrinol. Lett., 25, 14
Hegde, 2010, Cannabinoid receptor activation leads to massive mobilization of myeloid-derived suppressor cells with potent immunosuppressive properties, Eur. J. Immunol., 40, 3358, 10.1002/eji.201040667
Gabrilovich, 2009, Myeloid-derived suppressor cells as regulators of the immune system, Nat. Rev. Immunol., 9, 162, 10.1038/nri2506
Kusmartsev, 2004, Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species, J. Immunol., 172, 989, 10.4049/jimmunol.172.2.989
Pillay, 2012, A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1, J. Clin. Invest., 122, 327, 10.1172/JCI57990
Pillay, 2013, Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences, Cell. Mol. Life Sci., 70, 3813, 10.1007/s00018-013-1286-4
Borgelt, 2013, The pharmacologic and clinical effects of medical cannabis, Pharmacotherapy, 33, 195, 10.1002/phar.1187
Pandey, 2011, Targeting cannabinoid receptors as a novel approach in the treatment of graft-versus-host disease: evidence from an experimental murine model, J. Pharmacol. Exp. Ther., 338, 819, 10.1124/jpet.111.182717
Nagarkatti, 2010, Do cannabinoids have a therapeutic role in transplantation?, Trends Pharmacol. Sci., 31, 345, 10.1016/j.tips.2010.05.006
Pereira, 1990, Mechanism of action of cyclosporine A in vivo, II: T cell priming in vivo to alloantigen can be mediated by an IL-2-independent cyclosporine A-resistant pathway, J. Immunol., 144, 2109, 10.4049/jimmunol.144.6.2109
Schorlemmer, 1998, Regulation of alloreactivity in the popliteal lymph node assay by the new immunosuppressants: malononitrilamides, Transpl. Int., 11, S448, 10.1007/s001470050518
Chaudhuri, 1993, The stimulation by dendritic cells of host-versus-graft reactivity in vivo, Immunol. Cell Biol., 71, 527, 10.1038/icb.1993.58
Koch, 1990, Reduction in popliteal lymph node graft-versus-host reactivity by homologous and heterologous pregnancy serum, J. Reprod. Immunol., 18, 147, 10.1016/0165-0378(90)90013-V
Chen, 2003, A kinetic study of the murine mixed lymphocyte reaction by 5,6-carboxyfluorescein diacetate succinimidyl ester labeling, J. Immunol. Methods, 279, 123, 10.1016/S0022-1759(03)00236-9
Jackson, 2014, Characterization of endocannabinoid-mediated induction of myeloid-derived suppressor cells involving mast cells and MCP-1, J. Leukoc. Biol., 95, 609, 10.1189/jlb.0613350
Guan, 2009, Role of CD44 in the differentiation of Th1 and Th2 cells: CD44-deficiency enhances the development of Th2 effectors in response to sheep RBC and chicken ovalbumin, J. Immunol., 183, 172, 10.4049/jimmunol.0802325
Ma, 2012, Anti-Gr-1 antibody depletion fails to eliminate hepatic myeloid-derived suppressor cells in tumor-bearing mice, J. Leukoc. Biol., 92, 1199, 10.1189/jlb.0212059
Guan, 2012, Resveratrol prevents endothelial cells injury in high-dose interleukin-2 therapy against melanoma, PLoS One, 7, e35650, 10.1371/journal.pone.0035650
Billingham, 1951, The technique of free skin grafting in mammals, J. Exp. Biol., 28, 385, 10.1242/jeb.28.3.385
McKallip, 2005, Δ-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response, J. Immunol., 174, 3281, 10.4049/jimmunol.174.6.3281
Hegde, 2008, Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells, Mol. Pharmacol., 74, 20, 10.1124/mol.108.047035
Zhao, 2012, Critical role of proinflammatory cytokine IL-6 in allograft rejection and tolerance, Am. J. Transplant., 12, 90, 10.1111/j.1600-6143.2011.03770.x
LeCapitaine, 2011, Chronic Δ-9-tetrahydrocannabinol administration increases lymphocyte CXCR4 expression in rhesus macaques, J. Neuroimmune Pharmacol., 6, 540, 10.1007/s11481-011-9277-4
Krupnick, 2002, Mechanism of T cell-mediated endothelial apoptosis, Transplantation, 74, 871, 10.1097/00007890-200209270-00022
Rodriguez, 2007, L-arginine availability regulates T-lymphocyte cell-cycle progression, Blood, 109, 1568, 10.1182/blood-2006-06-031856
Sido, 2015, Δ9 Tetrahydrocannabinol-mediated epigenetic modifications elicit myeloid-derived suppressor cell activation via STAT3/S100A8, J. Leukoc. Biol˙., 97, 677, 10.1189/jlb.1A1014-479R
Movahedi, 2008, Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity, Blood, 111, 4233, 10.1182/blood-2007-07-099226
Dugast, 2008, Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion, J. Immunol., 180, 7898, 10.4049/jimmunol.180.12.7898
Semenov, 1990, [The Bristow-Latarjet operation in the treatment of habitual dislocation of the shoulder] [in Russian], Ortop. Travmatol. Protez.
Ostanin, 2013, Myeloid-derived suppressor cells in the inflammatory bowel diseases, Inflamm. Bowel Dis., 19, 2468, 10.1097/MIB.0b013e3182902b11
Ostrand-Rosenberg, 2012, Regulating the suppressors: apoptosis and inflammation govern the survival of tumor-induced myeloid-derived suppressor cells (MDSC), Cancer Immunol. Immunother., 61, 1319, 10.1007/s00262-012-1269-6
Jackson, 2014, Characterization of endocannabinoid-mediated induction of myeloid-derived suppressor cells involving mast cells and MCP-1, J. Leukoc. Biol., 95, 609, 10.1189/jlb.0613350
Huang, 2007, CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers, Cancer Lett., 252, 86, 10.1016/j.canlet.2006.12.012
Pandey, 2009, Use of cannabinoids as a novel therapeutic modality against autoimmune hepatitis, Vitam. Horm., 81, 487, 10.1016/S0083-6729(09)81019-4
Adams, 1996, Cannabis: pharmacology and toxicology in animals and humans, Addiction, 91, 1585, 10.1111/j.1360-0443.1996.tb02264.x
Croxford, 2005, Cannabinoids and the immune system: potential for the treatment of inflammatory diseases?, J. Neuroimmunol., 166, 3, 10.1016/j.jneuroim.2005.04.023
Massi, 2006, Cannabinoids, immune system and cytokine network, Curr. Pharm. Des., 12, 3135, 10.2174/138161206777947425
Ashton, 2007, Cannabinoids for the treatment of inflammation, Curr. Opin. Investig. Drugs, 8, 373
Yuan, 2002, Delta 9-Tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells, J. Neuroimmunol., 133, 124, 10.1016/S0165-5728(02)00370-3
Lombard, 2011, 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., 339, 607, 10.1124/jpet.111.181206
Rao, 2015, Δ9tetrahydrocannabinol attenuates Staphylococcal enterotoxin B-induced inflammatory lung injury and prevents mortality in mice by modulation of miR-17-92 cluster and induction of T-regulatory cells, Br. J. Pharmacol., 172, 1392, 10.1111/bph.13026
Young, 1987, Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors, Cancer Res., 47, 100
Zhang, 2014, mTOR limits the recruitment of CD11b+Gr1+Ly6Chigh myeloid-derived suppressor cells in protecting against murine immunological hepatic injury, J. Leukoc. Biol., 95, 961, 10.1189/jlb.0913473
De Wilde, 2009, Endotoxin-induced myeloid-derived suppressor cells inhibit alloimmune responses via heme oxygenase-1, Am. J. Transplant., 9, 2034, 10.1111/j.1600-6143.2009.02757.x
Highfill, 2010, Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13, Blood, 116, 5738, 10.1182/blood-2010-06-287839
McKallip, 2002, Δ9-tetrahydrocannabinol-induced apoptosis in the thymus and spleen as a mechanism of immunosuppression in vitro and in vivo, J. Pharmacol. Exp. Ther., 302, 451, 10.1124/jpet.102.033506
Jia, 2006, Δ9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria, Mol. Cancer Res., 4, 549, 10.1158/1541-7786.MCR-05-0193
Meyer, 2011, Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model, Proc. Natl. Acad. Sci. U. S. A., 108, 17111, 10.1073/pnas.1108121108
Robinson, 2013, Cannabinoids inhibit T-cells via cannabinoid receptor 2 in an in vitro assay for graft rejection, the mixed lymphocyte reaction, J. Neuroimmune Pharmacol., 8, 1239, 10.1007/s11481-013-9485-1
Gaffal, 2013, Cannabinoid 1 receptors in keratinocytes modulate proinflammatory chemokine secretion and attenuate contact allergic inflammation, J. Immunol., 190, 4929, 10.4049/jimmunol.1201777
Daaka, 1996, Cannabinoid receptor proteins are increased in Jurkat, human T-cell line after mitogen activation, J. Pharmacol. Exp. Ther., 276, 776
Duncan, 2013, Cannabinoid 1 receptors are critical for the innate immune response to TLR4 stimulation, Am. J. Physiol. Regul. Integr. Comp. Physiol., 305, R224, 10.1152/ajpregu.00104.2013
Börner, 2007, Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids, J. Leukoc. Biol., 81, 336, 10.1189/jlb.0306224
Massi, 1998, Immune function alterations in mice tolerant to delta9-tetrahydrocannabinol: functional and biochemical parameters, J. Neuroimmunol., 92, 60, 10.1016/S0165-5728(98)00177-5
Lu, 2009, Suppression of T cell costimulator ICOS by Δ9-tetrahydrocannabinol, J. Leukoc. Biol., 85, 322, 10.1189/jlb.0608390
Chuchawankul, 2004, Role of cannabinoid receptors in inhibiting macrophage costimulatory activity, Int. Immunopharmacol., 4, 265, 10.1016/j.intimp.2003.12.011
Jeon, 1996, Attenuation of inducible nitric oxide synthase gene expression by delta 9-tetrahydrocannabinol is mediated through the inhibition of nuclear factor- kappa B/Rel activation, Mol. Pharmacol., 50, 334
Annibaldi, 2008, CD28 ligation in the absence of TCR promotes RelA/NF-kappaB recruitment and trans-activation of the HIV-1 LTR, Eur. J. Immunol., 38, 1446, 10.1002/eji.200737854
Zhou, 2003, Impaired NF-κB activation in T cells permits tolerance to primary heart allografts and to secondary donor skin grafts, Am. J. Transplant., 3, 139, 10.1034/j.1600-6143.2003.00033.x
Ying, 2012, Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110δ prevents chronic rejection of heart allografts, PLoS One, 7, e32892, 10.1371/journal.pone.0032892
Joss, 2000, IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway, Eur. J. Immunol., 30, 1683, 10.1002/1521-4141(200006)30:6<1683::AID-IMMU1683>3.0.CO;2-A
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
Ongrádi, 1999, [Additive effect of marihuana and retrovirus in the anergy of natural killer cells in mice] [in Hungarian], Orv. Hetil., 140, 81