Immunoregulatory Effects of the Active Form of Vitamin D (Calcitriol), Individually and in Combination with Curcumin, on Peripheral Blood Mononuclear Cells (PBMCs) of Multiple Sclerosis (MS) Patients


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Objectives:Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate the disease process. Calcitriol, the active form of vitamin D, and curcumin, a bioactive compound derived from turmeric, play immunomodulatory effects relevant to autoimmune disorders, including MS. The objective of this study is to investigate the effects of calcitriol and Curcumin on Peripheral blood mononuclear cells (PBMCs) of individuals with MS.

Methods:PBMCs from twenty MS patients were isolated, cultured, and exposed to 0.004 µg/mL of calcitriol and 10 µg/mL of curcumin. The cells underwent treatment with singular or combined doses of these components to assess potential cumulative or synergistic immunomod-ulatory effects. Following treatment, the expression levels of genes and the cellular population of Treg, Th1 and Th17 were evaluated using Real-time PCR and flow cytometry.

Results:Treatment with curcumin and calcitriol led to a significant reduction in the expression levels of inflammatory cytokines and transcription factors related to Th1 and Th17 cells, including IFN-γ, T-bet, IL-17, and RORC. Furthermore, the frequency of these cells decreased following treatment. Additionally, curcumin and calcitriol treatment resulted in a significant upregulation of the FOXP3 gene expression and an increase in the frequency of Treg cells.

Conclusion:This study demonstrates that curcumin and calcitriol can effectively modulate the inflammatory processes intrinsic to MS by mitigating the expression of inflammatory cytokines by Th1 and Th17 cells while concurrently enhancing the regulatory role of Treg cells. Moreover, the combined treatment of curcumin and calcitriol did not yield superior outcomes compared to single-dosing strategies.

作者简介

Mahdieh Fasihi

Department of Immunology, School of Public Health, Tehran University of Medical Sciences

Email: info@benthamscience.net

Mahsa Samimi-Badabi

Department of Immunology, School of Public Health, Tehran University of Medical Sciences

Email: info@benthamscience.net

Behrouz Robat-Jazi

Department of Immunology, School of Public Health, Tehran University of Medical Sciences

Email: info@benthamscience.net

Sama Bitarafan

Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences

Email: info@benthamscience.net

Abdorreza Moghadasi

Department of Neurology and MS Research Center, Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences

Email: info@benthamscience.net

Fatemeh Mansouri

Department of Immunology, School of Public Health, Tehran University of Medical Sciences

Email: info@benthamscience.net

Mir Yekaninejad

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences

Email: info@benthamscience.net

Maryam Izad

Department of Immunology, School of Medicine, Tehran University of Medical Sciences

Email: info@benthamscience.net

Ali Saboor-Yaraghi

Department of Immunology, School of Public Health, Tehran University of Medical Sciences

编辑信件的主要联系方式.
Email: info@benthamscience.net

参考

  1. Chakamian, K.; Jazi, R.B.; Moghadasi, A.N.; Mansouri, F.; Nodehi, M.; Motevaseli, E.; Izad, M.; Yekaninejad, S.; Shirzad, M.; Bidad, K.; Oraei, M.; Ansaripour, B.; Yaraghi, S.A.A. Immunosuppressive effects of two probiotics, lactobacillus paracasei DSM 13434 and lactobacillus plantarum DSM 15312, on CD4+ T cells of multiple sclerosis patients. Iran. J. Allergy Asthma Immunol., 2023, 22(1), 34-45. doi: 10.18502/ijaai.v22i1.12004 PMID: 37002629
  2. Robat-Jazi, B.; Oraei, M.; Bitarafan, S.; Namin, M.S.A.; Zadeh, N.A.; Mansouri, F.; Parastouei, K.; Anissian, A.; Yekaninejad, M.S.; Yaraghi, S.A.A. Immunoregulatory effect of calcitriol on experimental autoimmune encephalomyelitis (EAE) mice. Iran. J. Allergy Asthma Immunol., 2023, 22(5), 452-467. PMID: 38085147
  3. Kubick, N.; Lazarczyk, M.; Strzałkowska, N.; Charuta, A.; Horbańczuk, J.O.; Sacharczuk, M.; Mickael, M.E. Factors regulating the differences in frequency of infiltration of Th17 and Treg of the blood–brain barrier. Immunogenetics, 2023, 75(5), 417-423. doi: 10.1007/s00251-023-01310-y PMID: 37430007
  4. Rostami, A.; Ciric, B. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination. J. Neurol. Sci., 2013, 333(1-2), 76-87. doi: 10.1016/j.jns.2013.03.002 PMID: 23578791
  5. Sakaguchi, S.; Ono, M.; Setoguchi, R.; Yagi, H.; Hori, S.; Fehervari, Z.; Shimizu, J.; Takahashi, T.; Nomura, T. Foxp3 + CD25 + CD4 + natural regulatory T cells in dominant self‐tolerance and autoimmune disease. Immunol. Rev., 2006, 212(1), 8-27. doi: 10.1111/j.0105-2896.2006.00427.x PMID: 16903903
  6. Costantino, C.M.; Allan, B.C.; Hafler, D.A. Multiple sclerosis and regulatory T cells. J. Clin. Immunol., 2008, 28(6), 697-706. doi: 10.1007/s10875-008-9236-x PMID: 18763026
  7. Venken, K.; Hellings, N.; Thewissen, M.; Somers, V.; Hensen, K.; Rummens, J.L.; Medaer, R.; Hupperts, R.; Stinissen, P. Compromised CD4 + CD25 high regulatory T‐cell function in patients with relapsing‐remitting multiple sclerosis is correlated with a reduced frequency of FOXP3‐positive cells and reduced FOXP3 expression at the single‐cell level. Immunology, 2008, 123(1), 79-89. doi: 10.1111/j.1365-2567.2007.02690.x PMID: 17897326
  8. Amalraj, A.; Pius, A.; Gopi, S.; Gopi, S. Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives – A review. J. Tradit. Complement. Med., 2017, 7(2), 205-233. doi: 10.1016/j.jtcme.2016.05.005 PMID: 28417091
  9. Ahmad, R.S.; Hussain, M.B.; Sultan, M.T.; Arshad, M.S.; Waheed, M.; Shariati, M.A.; Plygun, S.; Hashempur, M.H. Biochemistry, safety, pharmacological activities, and clinical applications of turmeric: A mechanistic review. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-14. doi: 10.1155/2020/7656919 PMID: 32454872
  10. Kocaadam, B.; Şanlier, N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit. Rev. Food Sci. Nutr., 2017, 57(13), 2889-2895. doi: 10.1080/10408398.2015.1077195 PMID: 26528921
  11. Xie, L.; Li, X.K.; Takahara, S. Curcumin has bright prospects for the treatment of multiple sclerosis. Int. Immunopharmacol., 2011, 11(3), 323-330. doi: 10.1016/j.intimp.2010.08.013 PMID: 20828641
  12. Lee, W.H.; Loo, C.Y.; Bebawy, M.; Luk, F.; Mason, R.; Rohanizadeh, R. Curcumin and its derivatives: Their application in neuropharmacology and neuroscience in the 21st century. Curr. Neuropharmacol., 2013, 11(4), 338-378. doi: 10.2174/1570159X11311040002 PMID: 24381528
  13. Yang, C.Y.; Leung, P.S.C.; Adamopoulos, I.E.; Gershwin, M.E. The implication of vitamin D and autoimmunity: A comprehensive review. Clin. Rev. Allergy Immunol., 2013, 45(2), 217-226. doi: 10.1007/s12016-013-8361-3 PMID: 23359064
  14. Robat-Jazi, B.; Mobini, S.; Chahardoli, R.; Mansouri, F.; Nodehi, M.; Esfahanian, F.; Yaraghi, S.A.A. The impact of vitamin D supplementation on the IFNγ-IP10 axis in women with hashimoto’s thyroiditis treated with levothyroxine: A double-blind randomized placebo-controlled trial. Iran. J. Allergy Asthma Immunol., 2022, 21(4), 407-417. doi: 10.18502/ijaai.v21i4.10288 PMID: 36243929
  15. Aranow, C. Vitamin D and the immune system. J. Investig. Med., 2011, 59(6), 881-886. doi: 10.2310/JIM.0b013e31821b8755 PMID: 21527855
  16. Bouillon, R.; Carmeliet, G.; Verlinden, L.; van Etten, E.; Verstuyf, A.; Luderer, H.F.; Lieben, L.; Mathieu, C.; Demay, M. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr. Rev., 2008, 29(6), 726-776. doi: 10.1210/er.2008-0004 PMID: 18694980
  17. Robat-Jazi, B.; Hosseini, M.; Shaygannejad, V.; Nafissi, S.; Rezaei, A.; Mansourain, M.; Mirmosayyeb, O.; Esmaeil, N. High frequency of Tc22 and Th22 cells in myasthenia gravis patients and their significant reduction after thymectomy. Neuroimmunomodulation, 2018, 25(2), 80-88. doi: 10.1159/000490855 PMID: 30071533
  18. Hosseini, M.; Jazi, R.B.; Shaygannejad, V.; Naffisi, S.; Mirmossayeb, O.; Rezaei, A.; Mansourian, M.; Esmaeil, N. Increased proportion of Tc17 and Th17 cells and their significant reduction after thymectomy may be related to disease progression in myasthenia gravis. Neuroimmunomodulation, 2017, 24(4-5), 264-270. doi: 10.1159/000486037 PMID: 29414833
  19. Tryfonos, C.; Mantzorou, M.; Fotiou, D.; Vrizas, M.; Vadikolias, K.; Pavlidou, E.; Giaginis, C. Dietary supplements on controlling multiple sclerosis symptoms and relapses: Current clinical evidence and future perspectives. Medicines , 2019, 6(3), 95. doi: 10.3390/medicines6030095 PMID: 31547410
  20. Gauzzi, M.C. Vitamin D-binding protein and multiple sclerosis: Evidence, controversies, and needs. Mult. Scler., 2018, 24(12), 1526-1535. doi: 10.1177/1352458518792433 PMID: 30113253
  21. Jagannath, V.A.; Filippini, G.; Di Pietrantonj, C.; Asokan, G.V.; Robak, E.W.; Whamond, L.; Robinson, S.A. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst. Rev., 2018, 9(9)CD008422 PMID: 30246874
  22. Dobson, R.; Cock, H.R.; Brex, P.; Giovannoni, G. Vitamin D supplementation. Pract. Neurol., 2018, 18(1), 35-42. doi: 10.1136/practneurol-2017-001720 PMID: 28947637
  23. Sintzel, M.B.; Rametta, M.; Reder, A.T. Vitamin D and multiple sclerosis: A comprehensive review. Neurol. Ther., 2018, 7(1), 59-85. doi: 10.1007/s40120-017-0086-4 PMID: 29243029
  24. Smolders, J.; Torkildsen, Ø.; Camu, W.; Holmøy, T. An update on vitamin D and disease activity in multiple sclerosis. CNS Drugs, 2019, 33(12), 1187-1199. doi: 10.1007/s40263-019-00674-8 PMID: 31686407
  25. Zhang, X.; Ge, R.; Chen, H.; Ahiafor, M.; Liu, B.; Chen, J.; Fan, X. Follicular helper CD4+ T cells, follicular regulatory CD4+ T cells, and inducible costimulator and their roles in multiple sclerosis and experimental autoimmune encephalomyelitis. Mediators Inflamm., 2021, 2021, 1-10. doi: 10.1155/2021/2058964 PMID: 34552387
  26. Wing, J.B.; Tanaka, A.; Sakaguchi, S. Human FOXP3+ regulatory T cell heterogeneity and function in autoimmunity and cancer. Immunity, 2019, 50(2), 302-316. doi: 10.1016/j.immuni.2019.01.020 PMID: 30784578
  27. Scheinecker, C.; Göschl, L.; Bonelli, M. Treg cells in health and autoimmune diseases: New insights from single cell analysis. J. Autoimmun., 2020, 110102376 doi: 10.1016/j.jaut.2019.102376 PMID: 31862128
  28. Sun, C.M.; Hall, J.A.; Blank, R.B.; Bouladoux, N.; Oukka, M.; Mora, J.R.; Belkaid, Y. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med., 2007, 204(8), 1775-1785. doi: 10.1084/jem.20070602 PMID: 17620362
  29. Huan, J.; Culbertson, N.; Spencer, L.; Bartholomew, R.; Burrows, G.G.; Chou, Y.K.; Bourdette, D.; Ziegler, S.F.; Offner, H.; Vandenbark, A.A. Decreased FOXP3 levels in multiple sclerosis patients. J. Neurosci. Res., 2005, 81(1), 45-52. doi: 10.1002/jnr.20522 PMID: 15952173
  30. Libera, D.D.; Di Mitri, D.; Bergami, A.; Centonze, D.; Gasperini, C.; Grasso, M.G.; Galgani, S.; Martinelli, V.; Comi, G.; Avolio, C.; Martino, G.; Borsellino, G.; Sallusto, F.; Battistini, L.; Furlan, R. T regulatory cells are markers of disease activity in multiple sclerosis patients. PLoS One, 2011, 6(6)e21386 doi: 10.1371/journal.pone.0021386 PMID: 21731726
  31. Sakaguchi, S.; Yamaguchi, T.; Nomura, T.; Ono, M. Regulatory T cells and immune tolerance. Cell, 2008, 133(5), 775-787. doi: 10.1016/j.cell.2008.05.009 PMID: 18510923
  32. Fontenot, J.D.; Gavin, M.A.; Rudensky, A.Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol., 2003, 4(4), 330-336. doi: 10.1038/ni904 PMID: 12612578
  33. Hori, S.; Nomura, T.; Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science, 2003, 299(5609), 1057-1061. doi: 10.1126/science.1079490 PMID: 12522256
  34. Khattri, R.; Cox, T.; Yasayko, S.A.; Ramsdell, F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol., 2003, 4(4), 337-342. doi: 10.1038/ni909 PMID: 12612581
  35. Deng, G.; Song, X.; Fujimoto, S.; Piccirillo, C.A.; Nagai, Y.; Greene, M.I. Foxp3 post-translational modifications and treg suppressive activity. Front. Immunol., 2019, 10, 2486. doi: 10.3389/fimmu.2019.02486 PMID: 31681337
  36. von Knethen, A.; Heinicke, U.; Weigert, A.; Zacharowski, K.; Brüne, B. Histone deacetylation inhibitors as modulators of regulatory T cells. Int. J. Mol. Sci., 2020, 21(7), 2356. doi: 10.3390/ijms21072356 PMID: 32235291
  37. Palomares, O.; Elewaut, D.; Irving, P.M.; Jaumont, X.; Tassinari, P. Regulatory T cells and immunoglobulin E: A new therapeutic link for autoimmunity? Allergy, 2022, 77(11), 3293-3308. doi: 10.1111/all.15449 PMID: 35852798
  38. Danikowski, K.M.; Jayaraman, S.; Prabhakar, B.S. Regulatory T cells in multiple sclerosis and myasthenia gravis. J. Neuroinflammation, 2017, 14(1), 117. doi: 10.1186/s12974-017-0892-8 PMID: 28599652
  39. Viglietta, V.; Baecher-Allan, C.; Weiner, H.L.; Hafler, D.A. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med., 2004, 199(7), 971-979. doi: 10.1084/jem.20031579 PMID: 15067033
  40. Haas, J.; Hug, A.; Viehöver, A.; Fritzsching, B.; Falk, C.S.; Filser, A.; Vetter, T.; Milkova, L.; Korporal, M.; Fritz, B.; Hagenlocher, S.B.; Krammer, P.H.; Suri-Payer, E.; Wildemann, B. Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol., 2005, 35(11), 3343-3352. doi: 10.1002/eji.200526065 PMID: 16206232
  41. Moser, T.; Akgün, K.; Proschmann, U.; Sellner, J.; Ziemssen, T. The role of TH17 cells in multiple sclerosis: Therapeutic implications. Autoimmun. Rev., 2020, 19(10)102647 doi: 10.1016/j.autrev.2020.102647 PMID: 32801039
  42. Kamali, A.N.; Noorbakhsh, S.M.; Hamedifar, H.; Niaragh, J.F.; Yazdani, R.; Bautista, J.M.; Azizi, G. A role for Th1-like Th17 cells in the pathogenesis of inflammatory and autoimmune disorders. Mol. Immunol., 2019, 105, 107-115. doi: 10.1016/j.molimm.2018.11.015 PMID: 30502718
  43. Melnikov, M.; Lopatina, A. Th17-cells in depression: Implication in multiple sclerosis. Front. Immunol., 2022, 131010304 doi: 10.3389/fimmu.2022.1010304 PMID: 36189272
  44. Melnikov, M.; Rogovskii, V.; Boyko, A.; Pashenkov, M. Dopaminergic therapeutics in multiple sclerosis: Focus on Th17-cell functions. J. Neuroimmune Pharmacol., 2020, 15(1), 37-47. doi: 10.1007/s11481-019-09852-3 PMID: 31011885
  45. Yang, J.; Sundrud, M.S.; Skepner, J.; Yamagata, T. Targeting Th17 cells in autoimmune diseases. Trends Pharmacol. Sci., 2014, 35(10), 493-500. doi: 10.1016/j.tips.2014.07.006 PMID: 25131183
  46. Kumar, R.; Theiss, A.L.; Venuprasad, K. RORγt protein modifications and IL-17-mediated inflammation. Trends Immunol., 2021, 42(11), 1037-1050. doi: 10.1016/j.it.2021.09.005 PMID: 34635393
  47. Balasa, R.; Barcutean, L.; Balasa, A.; Motataianu, A.; Filip, R.C.; Manu, D. The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis. Hum. Immunol., 2020, 81(5), 237-243. doi: 10.1016/j.humimm.2020.02.009 PMID: 32122685
  48. Ntolkeras, G.; Barba, C.; Mavropoulos, A.; Vasileiadis, G.K.; Dardiotis, E.; Sakkas, L.I.; Hadjigeorgiou, G.; Bogdanos, D.P. On the immunoregulatory role of statins in multiple sclerosis: the effects on Th17 cells. Immunol. Res., 2019, 67(4-5), 310-324. doi: 10.1007/s12026-019-09089-5 PMID: 31399952
  49. Melnikov, M.; Rogovskii, V.; Boyko, A.; Pashenkov, M. The influence of biogenic amines on Th17-mediated immune response in multiple sclerosis. Mult. Scler. Relat. Disord., 2018, 21, 19-23. doi: 10.1016/j.msard.2018.02.012 PMID: 29454152
  50. McGinley, A.M.; Edwards, S.C.; Raverdeau, M.; Mills, K.H.G. Th17 cells, γδ T cells and their interplay in EAE and multiple sclerosis. J. Autoimmun., 2018, 87, 97-108. doi: 10.1016/j.jaut.2018.01.001 PMID: 29395738
  51. Melnikov, M.; Pashenkov, M.; Boyko, A. Dopaminergic receptor targeting in multiple sclerosis: Is there therapeutic potential? Int. J. Mol. Sci., 2021, 22(10), 5313. doi: 10.3390/ijms22105313 PMID: 34070011
  52. Chen, C.; Zhou, Y.; Wang, J.; Yan, Y.; Peng, L.; Qiu, W. Dysregulated MicroRNA involvement in multiple sclerosis by induction of T helper 17 cell differentiation. Front. Immunol., 2018, 9, 1256. doi: 10.3389/fimmu.2018.01256 PMID: 29915595
  53. Joshi, S.; Pantalena, L.C.; Liu, X.K.; Gaffen, S.L.; Liu, H.; Kochan, C.; Ichiyama, K.; Yoshimura, A.; Steinman, L.; Christakos, S.; Youssef, S. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol. Cell. Biol., 2011, 31(17), 3653-3669. doi: 10.1128/MCB.05020-11 PMID: 21746882
  54. Zeitelhofer, M.; Adzemovic, M.Z.; Cabrero, G.D.; Bergman, P.; Hochmeister, S.; N’diaye, M.; Paulson, A.; Ruhrmann, S.; Almgren, M.; Tegnér, J.N.; Ekström, T.J.; Cacais, G.A.O.; Jagodic, M. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci., 2017, 114(9), E1678-E1687. doi: 10.1073/pnas.1615783114 PMID: 28196884
  55. Mahler, J.V.; Solti, M.; Pereira, A.S.L.; Adoni, T.; Silva, G.D.; Callegaro, D. Vitamin D3 as an add-on treatment for multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials. Mult. Scler. Relat. Disord., 2024, 82105433 doi: 10.1016/j.msard.2024.105433 PMID: 38211504
  56. Butzkueven, H.; Ponsonby, A.L.; Stein, M.S.; Lucas, R.M.; Mason, D.; Broadley, S.; Kilpatrick, T.; Scott, L.J.; Barnett, M.; Carroll, W.; Mitchell, P.; Hardy, T.A.; Macdonell, R.; McCombe, P.; Lee, A.; Kalincik, T.; van der Walt, A.; Lynch, C.; Abernethy, D.; Willoughby, E.; Barkhof, F.; MacManus, D.; Clarke, M.; Andrew, J.; Morahan, J.; Zhu, C.; Dear, K.; Taylor, B.V. Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome. Brain, 2023, 2023awad409 doi: 10.1093/brain/awad409 PMID: 38085047
  57. Cassard, S.D.; Fitzgerald, K.C.; Qian, P.; Emrich, S.A.; Azevedo, C.J.; Goodman, A.D.; Sugar, E.A.; Pelletier, D.; Waubant, E.; Mowry, E.M. High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: A randomised clinical trial. EClinicalMedicine, 2023, 59101957 doi: 10.1016/j.eclinm.2023.101957 PMID: 37125397
  58. Handono, K.; Pratama, M.Z.; Endharti, A.T.; Kalim, H. Treatment of low doses curcumin could modulate Th17/Treg balance specifically on CD4+ T cell cultures of systemic lupus erythematosus patients. Cent. Eur. J. Immunol., 2015, 4(4), 461-469. doi: 10.5114/ceji.2015.56970 PMID: 26862311
  59. Liu, X.; Lee, Y.S.; Yu, C.R.; Egwuagu, C.E. Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases. J. Immunol., 2008, 180(9), 6070-6076. doi: 10.4049/jimmunol.180.9.6070 PMID: 18424728
  60. Kim, H.Y.; Park, E.J.; Joe, E.; Jou, I. Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J. Immunol., 2003, 171(11), 6072-6079. doi: 10.4049/jimmunol.171.11.6072 PMID: 14634121
  61. Xie, L.; Li, X.K.; Fuji, F.N.; Kimura, H.; Matsumoto, Y.; Isaka, Y.; Takahara, S. Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int. Immunopharmacol., 2009, 9(5), 575-581. doi: 10.1016/j.intimp.2009.01.025 PMID: 19539560
  62. Bharti, A.C.; Donato, N.; Aggarwal, B.B. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J. Immunol., 2003, 171(7), 3863-3871. doi: 10.4049/jimmunol.171.7.3863 PMID: 14500688

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