Generic placeholder image

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

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

Author(s): Mahdieh Fasihi, Mahsa Samimi-Badabi, Behrouz Robat-Jazi, Sama Bitarafan, Abdorreza Naser Moghadasi, Fatemeh Mansouri, Mir Saeed Yekaninejad, Maryam Izad and Ali Akbar Saboor-Yaraghi*

Volume 23, Issue 2, 2024

Published on: 01 April, 2024

Page: [138 - 147] Pages: 10

DOI: 10.2174/0118715230293847240314073359

Price: $65

Abstract

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 immunomodulatory 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.

Graphical Abstract

[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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.18502/ijaai.v21i4.10288 ] [PMID: 36243929]
[15]
Aranow, C. Vitamin D and the immune system. J. Investig. Med., 2011, 59(6), 881-886.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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
[http://dx.doi.org/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.
[http://dx.doi.org/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
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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
[http://dx.doi.org/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
[http://dx.doi.org/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
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.4049/jimmunol.171.7.3863 ] [PMID: 14500688]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy