Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Vitamin D Levels Correlate with Metabolic Syndrome Criteria in Algerian Patients: The Ex-vivo Immunomodulatory Effect of α, 25 Dihydroxyvitamin D3

Author(s): Meroua Bouchemal, Djennat Hakem, Malha Azzouz, Chafia Touil-Boukoffa and Dalila Mezioug*

Volume 20, Issue 8, 2020

Page: [1282 - 1294] Pages: 13

DOI: 10.2174/1871530320666200402121917

Price: $65

Abstract

Background: Metabolic syndrome (MetS) is a combination of metabolic disorders with increased risks for several diseases, such as cardiovascular diseases and diabetes. It is associated with the presence of various inflammatory molecules. Vitamin D plays an important role in the regulation of metabolism homeostasis.

Objective: The main goal of this work is to investigate vitamin D levels among Algerian MetS patients and its possible outcomes on key molecules of the immune response, as well, the immunomodulatory effects of its active metabolite.

Methods: We evaluated vitamin D status by the electrochemiluminescence method, Nitric Oxide (NO) levels by the Griess method and Matrix Metalloproteinases (MMPs) activities such as MMP-2 and MMP-9 by zymography in plasma of patients and healthy controls (HC). The immunomodulatory effects of the active metabolite of vitamin D (α-25 (OH)2D3) on the production of NO, IL-6, IL-10, TGF- β and s-CTLA-4 were assessed by Griess method and ELISA, in peripheral blood mononuclear cells (PBMCs) of Algerian MetS patients and HC. MMPs activities were also determined ex-vivo, while iNOS expression was assessed by immunofluorescence staining.

Results: Severe vitamin D deficiency was registered in Algerian MetS patients. The deficiency was found to be associated with an elevated in vivo NO production and high MMPs activity. Interestingly, α-25 (OH)2D3 declined the NO/iNOS system and IL-6 production, as well as MMPs activities. However, the ex-vivo production of IL-10, TGF-β increased in response to the treatment. We observed in the same way, the implication of s-CTLA-4 in MetS, which was markedly up-regulated with α-25 (OH)2D3.

Conclusion: Our report indicated the relationship between MetS factors and Vitamin D deficiency. The ex-vivo findings emphasize its impact on maintaining regulated immune balance.

Keywords: Metabolic syndrome, vitamin D, nitric oxide, metalloproteinases, cytokines, CTLA-4.

« Previous Next »
Graphical Abstract

[1]
Alberti, K.G.M.; Zimmet, P.; Shaw, J. The metabolic syndrome--a new worldwide definition. Lancet, 2005, 366(9491), 1059-1062.
[http://dx.doi.org/10.1016/S0140-6736(05)67402-8] [PMID: 16182882]
[2]
Isomaa, B.; Almgren, P.; Tuomi, T.; Forsén, B.; Lahti, K.; Nissén, M.; Taskinen, M-R.; Groop, L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care, 2001, 24(4), 683-689.
[http://dx.doi.org/10.2337/diacare.24.4.683] [PMID: 11315831]
[3]
Ordovas, J.M.; Shen, J. Gene-environment interactions and susceptibility to metabolic syndrome and other chronic diseases. J. Periodontol., 2008, 79(Suppl. 8), 1508-1513.
[http://dx.doi.org/10.1902/jop.2008.080232] [PMID: 18673004]
[4]
Cheung, N.; Wang, J.J.; Rogers, S.L.; Brancati, F.; Klein, R.; Sharrett, A.R.; Wong, T.Y. Diabetic retinopathy and risk of heart failure. J. Am. Coll. Cardiol., 2008, 51(16), 1573-1578.
[http://dx.doi.org/10.1016/j.jacc.2007.11.076] [PMID: 18420100]
[5]
Fantuzzi, G. Adipose tissue, adipokines, and inflammation. J. Allergy Clin. Immunol., 2005, 115(5), 911-919.
[http://dx.doi.org/10.1016/j.jaci.2005.02.023] [PMID: 15867843]
[6]
Gross, S.S.; Wolin, M.S. Nitric oxide: pathophysiological mechanisms. Annu. Rev. Physiol., 1995, 57(1), 737-769.
[http://dx.doi.org/10.1146/annurev.ph.57.030195.003513] [PMID: 7539995]
[7]
Adams, V.; Nehrhoff, B.; Späte, U.; Linke, A.; Schulze, P.C.; Baur, A.; Gielen, S.; Hambrecht, R.; Schuler, G. Induction of iNOS expression in skeletal muscle by IL-1β and NFkappaB activation: an in vitro and in vivo study. Cardiovasc. Res., 2002, 54(1), 95-104.
[http://dx.doi.org/10.1016/S0008-6363(02)00228-6] [PMID: 12062366]
[8]
Serbina, N.V.; Salazar-Mather, T.P.; Biron, C.A.; Kuziel, W.A.; Pamer, E.G. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity, 2003, 19(1), 59-70.
[http://dx.doi.org/10.1016/S1074-7613(03)00171-7] [PMID: 12871639]
[9]
Kim, J.A.; Montagnani, M.; Koh, K.K.; Quon, M.J. Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms. Circulation, 2006, 113(15), 1888-1904.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.563213] [PMID: 16618833]
[10]
Adlam, D.; Bendall, J.K.; De Bono, J.P.; Alp, N.J.; Khoo, J.; Nicoli, T.; Yokoyama, M.; Kawashima, S.; Channon, K.M. Relationships between nitric oxide-mediated endothelial function, eNOS coupling and blood pressure revealed by eNOS-GTP cyclohydrolase 1 double transgenic mice. Exp. Physiol., 2007, 92(1), 119-126.
[http://dx.doi.org/10.1113/expphysiol.2006.035113] [PMID: 17012144]
[11]
Chavey, C.; Mari, B.; Monthouel, M-N.; Bonnafous, S.; Anglard, P.; Van Obberghen, E.; Tartare-Deckert, S. Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J. Biol. Chem., 2003, 278(14), 11888-11896.
[http://dx.doi.org/10.1074/jbc.M209196200] [PMID: 12529376]
[12]
Stamenkovic, I. Extracellular matrix remodelling: The role of matrix metalloproteinases. J. Pathol., 2003, 200(4), 448-464.
[13]
Miksztowicz, V.; Muzzio, M.L.; Royer, M.; Prada, M.; Wikinski, R.; Schreier, L.; Berg, G. Increased plasma activity of metalloproteinase 2 in women with metabolic syndrome. Metabolism, 2008, 57(11), 1493-1496.
[http://dx.doi.org/10.1016/j.metabol.2008.06.001] [PMID: 18940384]
[14]
Hotamisligil, G.S. Inflammation and metabolic disorders. Nature, 2006, 444(7121), 860-867.
[http://dx.doi.org/10.1038/nature05485] [PMID: 17167474]
[15]
Cottam, D.R.; Mattar, S.G.; Barinas-Mitchell, E.; Eid, G.; Kuller, L.; Kelley, D.E.; Schauer, P.R. The chronic inflammatory hypothesis for the morbidity associated with morbid obesity: implications and effects of weight loss. Obes. Surg., 2004, 14(5), 589-600.
[http://dx.doi.org/10.1381/096089204323093345] [PMID: 15186624]
[16]
Damle, N.K.; Klussman, K.; Leytze, G.; Myrdal, S.; Aruffo, A.; Ledbetter, J.A.; Linsley, P.S. Costimulation of T lymphocytes with integrin ligands intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 induces functional expression of CTLA-4, a second receptor for B7. J. Immunol., 1994, 152(6), 2686-2697.
[PMID: 7511623]
[17]
Fife, B.T.; Bluestone, J.A. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol. Rev., 2008, 224(1), 166-182.
[http://dx.doi.org/10.1111/j.1600-065X.2008.00662.x] [PMID: 18759926]
[18]
Cantorna, M.T. Vitamin D and its role in immunology: Multiple sclerosis, and inflammatory bowel disease. Prog. Biophys. Mol. Biol., 2006, 92(1), 60-64.
[http://dx.doi.org/10.1016/j.pbiomolbio.2006.02.020] [PMID: 16563470]
[19]
Rammos, G.; Tseke, P.; Ziakka, S.; Vitamin, D. Vitamin D, the renin-angiotensin system, and insulin resistance. Int. Urol. Nephrol., 2008, 40(2), 419-426.
[http://dx.doi.org/10.1007/s11255-007-9244-4] [PMID: 18193490]
[20]
Barthel, T.K.; Mathern, D.R.; Whitfield, G.K.; Haussler, C.A.; Hopper, H.A., IV; Hsieh, J-C.; Slater, S.A.; Hsieh, G.; Kaczmarska, M.; Jurutka, P.W.; Kolek, O.I.; Ghishan, F.K.; Haussler, M.R. 1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J. Steroid Biochem. Mol. Biol., 2007, 103(3-5), 381-388.
[http://dx.doi.org/10.1016/j.jsbmb.2006.12.054] [PMID: 17293108]
[21]
Haussler, M.R.; Whitfield, G.K.; Haussler, C.A.; Hsieh, J.C.; Thompson, P.D.; Selznick, S.H.; Dominguez, C.E.; Jurutka, P.W. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J. Bone Miner. Res., 1998, 13(3), 325-349.
[http://dx.doi.org/10.1359/jbmr.1998.13.3.325] [PMID: 9525333]
[22]
Fawaz, L.; Mrad, M.F.; Kazan, J.M.; Sayegh, S.; Akika, R.; Khoury, S.J. Comparative effect of 25(OH)D3 and 1,25(OH)2D3 on Th17 cell differentiation. Clin. Immunol., 2016, 166-167, 59-71.
[http://dx.doi.org/10.1016/j.clim.2016.02.011] [PMID: 27041081]
[23]
Ross, A.C. The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr., 2011, 14(5), 938-939.
[http://dx.doi.org/10.1017/S1368980011000565] [PMID: 21492489]
[24]
Mezioug, D.; Touil-Boukoffa, C. Interleukin-17A correlates with interleukin-6 production in human cystic echinococcosis: a possible involvement of IL-17A in immunoprotection against Echinococcus granulosus infection. Eur. Cytokine Netw., 2012, 23(3), 112-119.
[http://dx.doi.org/10.1684/ecn.2012.0314] [PMID: 23009764]
[25]
Kennel, K.A. Drake, M. T.; Hurley, D. L.Vitamin D deficiency in adults: when to test and how to treat, Mayo Clinic Proceedings; Elsevier, 2010, pp. 752-758.
[26]
Holick, M.F. Vitamin D deficiency. N. Engl. J. Med., 2007, 357(3), 266-281.
[http://dx.doi.org/10.1056/NEJMra070553] [PMID: 17634462]
[27]
van Etten, E.; Mathieu, C. Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts. J. Steroid Biochem. Mol. Biol., 2005, 97(1-2), 93-101.
[http://dx.doi.org/10.1016/j.jsbmb.2005.06.002] [PMID: 16046118]
[28]
Boonstra, A.; Barrat, F.J.; Crain, C.; Heath, V.L.; Savelkoul, H.F.; O’Garra, A. 1α,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J. Immunol., 2001, 167(9), 4974-4980.
[http://dx.doi.org/10.4049/jimmunol.167.9.4974] [PMID: 11673504]
[29]
Targher, G.; Bertolini, L.; Scala, L.; Cigolini, M.; Zenari, L.; Falezza, G.; Arcaro, G. Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr. Metab. Cardiovasc. Dis., 2007, 17(7), 517-524.
[http://dx.doi.org/10.1016/j.numecd.2006.04.002] [PMID: 16928437]
[30]
Botella-Carretero, J.I.; Alvarez-Blasco, F.; Villafruela, J.J.; Balsa, J.A.; Vázquez, C.; Escobar-Morreale, H.F. Vitamin D deficiency is associated with the metabolic syndrome in morbid obesity. Clin. Nutr., 2007, 26(5), 573-580.
[http://dx.doi.org/10.1016/j.clnu.2007.05.009] [PMID: 17624643]
[31]
Cigolini, M.; Iagulli, M.P.; Miconi, V.; Galiotto, M.; Lombardi, S.; Targher, G. Serum 25-hydroxyvitamin D3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care, 2006, 29(3), 722-724.
[http://dx.doi.org/10.2337/diacare.29.03.06.dc05-2148] [PMID: 16505539]
[32]
Ford, E.S.; Ajani, U.A.; McGuire, L.C.; Liu, S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care, 2005, 28(5), 1228-1230.
[http://dx.doi.org/10.2337/diacare.28.5.1228] [PMID: 15855599]
[33]
Hyppönen, E.; Boucher, B.J.; Berry, D.J.; Power, C. 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes, 2008, 57(2), 298-305.
[http://dx.doi.org/10.2337/db07-1122] [PMID: 18003755]
[34]
Cheng, S.; Massaro, J.M.; Fox, C.S.; Larson, M.G.; Keyes, M.J.; McCabe, E.L.; Robins, S.J.; O’Donnell, C.J.; Hoffmann, U.; Jacques, P.F.; Booth, S.L.; Vasan, R.S.; Wolf, M.; Wang, T.J. Adiposity, cardiometabolic risk, and vitamin D status: The Framingham Heart Study. Diabetes, 2010, 59(1), 242-248.
[http://dx.doi.org/10.2337/db09-1011] [PMID: 19833894]
[35]
Rosenblum, J.L.; Castro, V.M.; Moore, C.E.; Kaplan, L.M. Calcium and vitamin D supplementation is associated with decreased abdominal visceral adipose tissue in overweight and obese adults. Am. J. Clin. Nutr., 2012, 95(1), 101-108.
[http://dx.doi.org/10.3945/ajcn.111.019489] [PMID: 22170363]
[36]
Maestro, B.; Campión, J.; Dávila, N.; Calle, C. Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr. J., 2000, 47(4), 383-391.
[http://dx.doi.org/10.1507/endocrj.47.383] [PMID: 11075718]
[37]
Zhang, C.; Qiu, C.; Hu, F.B.; David, R.M.; van Dam, R.M.; Bralley, A.; Williams, M.A. Maternal plasma 25-hydroxyvitamin D concentrations and the risk for gestational diabetes mellitus. PLoS One, 2008, 3(11), e3753.
[http://dx.doi.org/10.1371/journal.pone.0003753] [PMID: 19015731]
[38]
Alvarez, J.A.; Ashraf, A. Role of vitamin D in insulin secretion and insulin sensitivity for glucose homeostasis. Nat. Rev. Endocrinol., 2010, 10(6), 364.
[http://dx.doi.org/10.1155/2010/351385]
[39]
DeMarco, V.G.; Aroor, A.R.; Sowers, J.R. The pathophysiology of hypertension in patients with obesity. Nat. Rev. Endocrinol., 2014, 10(6), 364-376.
[http://dx.doi.org/10.1038/nrendo.2014.44] [PMID: 24732974]
[40]
Fulton, D.; Gratton, J-P.; McCabe, T.J.; Fontana, J.; Fujio, Y.; Walsh, K.; Franke, T.F.; Papapetropoulos, A.; Sessa, W.C. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature, 1999, 399(6736), 597-601.
[http://dx.doi.org/10.1038/21218] [PMID: 10376602]
[41]
Aktan, F. iNOS-mediated nitric oxide production and its regulation. Life Sci., 2004, 75(6), 639-653.
[http://dx.doi.org/10.1016/j.lfs.2003.10.042] [PMID: 15172174]
[42]
Kleinert, H.; Art, J.; Pautz, A. Regulation of the expression of inducible nitric oxide synthase.Nitric Oxide; Elsevier, 2010, pp. 211-267.
[http://dx.doi.org/10.1016/B978-0-12-373866-0.00007-1]
[43]
Chang, P.C.; Chen, T.H.; Chang, C.J.; Hou, C.C.; Chan, P.; Lee, H.M. Advanced glycosylation end products induce inducible nitric oxide synthase (iNOS) expression via a p38 MAPK-dependent pathway. Kidney Int., 2004, 65(5), 1664-1675.
[http://dx.doi.org/10.1111/j.1523-1755.2004.00602.x] [PMID: 15086905]
[44]
Yammani, R.R.; Carlson, C.S.; Bresnick, A.R.; Loeser, R.F. Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: Role of the receptor for advanced glycation end products. Arthritis Rheum., 2006, 54(9), 2901-2911.
[http://dx.doi.org/10.1002/art.22042] [PMID: 16948116]
[45]
Hopps, E.; Caimi, G. Matrix metalloproteinases in metabolic syndrome. Eur. J. Intern. Med., 2012, 23(2), 99-104.
[http://dx.doi.org/10.1016/j.ejim.2011.09.012] [PMID: 22284236]
[46]
Scroyen, I.; Cosemans, L.; Lijnen, H.R. Effect of tissue inhibitor of matrix metalloproteinases-1 on in vitro and in vivo adipocyte differentiation. Thromb. Res., 2009, 124(5), 578-583.
[http://dx.doi.org/10.1016/j.thromres.2009.06.020] [PMID: 19608218]
[47]
Friese, R. S.; Rao, F.; Khandrika, S.; Thomas, B.; Ziegler, M. G.; Schmid-Schonbein, G. W.; O'Connor, D. T. Matrix metalloproteinases: discrete elevations in essential hypertension and hypertensive end-stage renal disease., Clinical and experimental hypertension (New York, N.Y.: 1993), 2009, 31(7), 521-33.
[48]
Selvin, E.; Marinopoulos, S.; Berkenblit, G.; Rami, T.; Brancati, F.L.; Powe, N.R.; Golden, S.H. Meta-analysis: Glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann. Intern. Med., 2004, 141(6), 421-431.
[http://dx.doi.org/10.7326/0003-4819-141-6-200409210-00007] [PMID: 15381515]
[49]
Miksztowicz, V.; Morales, C.; Zago, V.; Friedman, S.; Schreier, L.; Berg, G. Effect of insulin-resistance on circulating and adipose tissue MMP-2 and MMP-9 activity in rats fed a sucrose-rich diet. Nutr. Metab. Cardiovasc. Dis., 2014, 24(3), 294-300.
[http://dx.doi.org/10.1016/j.numecd.2013.08.007] [PMID: 24418386]
[50]
Viappiani, S.; Nicolescu, A.C.; Holt, A.; Sawicki, G.; Crawford, B.D.; León, H.; van Mulligen, T.; Schulz, R. Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione. Biochem. Pharmacol., 2009, 77(5), 826-834.
[http://dx.doi.org/10.1016/j.bcp.2008.11.004] [PMID: 19046943]
[51]
Rajagopalan, S.; Meng, X.P.; Ramasamy, S.; Harrison, D.G.; Galis, Z.S. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J. Clin. Invest., 1996, 98(11), 2572-2579.
[http://dx.doi.org/10.1172/JCI119076] [PMID: 8958220]
[52]
Van Wart, H.E.; Birkedal-Hansen, H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc. Natl. Acad. Sci. USA, 1990, 87(14), 5578-5582.
[http://dx.doi.org/10.1073/pnas.87.14.5578] [PMID: 2164689]
[53]
Chandrasekar, B.; Mummidi, S.; Mahimainathan, L.; Patel, D.N.; Bailey, S.R.; Imam, S.Z.; Greene, W.C.; Valente, A.J. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. J. Biol. Chem., 2006, 281(22), 15099-15109.
[http://dx.doi.org/10.1074/jbc.M600200200] [PMID: 16554298]
[54]
Sugiura, H.; Kawabata, H.; Ichikawa, T.; Koarai, A.; Yanagisawa, S.; Kikuchi, T.; Minakata, Y.; Matsunaga, K.; Nakanishi, M.; Hirano, T.; Akamatsu, K.; Furukawa, K.; Ichinose, M. Inhibitory effects of theophylline on the peroxynitrite-augmented release of matrix metalloproteinases by lung fibroblasts. Am. J. Physiol. Lung Cell. Mol. Physiol., 2012, 302(8), L764-L774.
[http://dx.doi.org/10.1152/ajplung.00342.2011] [PMID: 22287608]
[55]
Muthian, G.; Raikwar, H.P.; Rajasingh, J.; Bright, J.J. 1,25 Dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis leading to Th1 response in experimental allergic encephalomyelitis. J. Neurosci. Res., 2006, 83(7), 1299-1309.
[http://dx.doi.org/10.1002/jnr.20826] [PMID: 16547967]
[56]
Mutt, S.J.; Karhu, T.; Lehtonen, S.; Lehenkari, P.; Carlberg, C.; Saarnio, J.; Sebert, S.; Hyppönen, E.; Järvelin, M-R.; Herzig, K-H. Inhibition of cytokine secretion from adipocytes by 1,25-dihydroxyvitamin D3 via the NF-κB pathway. FASEB J., 2012, 26(11), 4400-4407.
[http://dx.doi.org/10.1096/fj.12-210880] [PMID: 22798425]
[57]
Wasse, H.; Cardarelli, F.; De Staercke, C.; Hooper, C.; Veledar, E.; Guessous, I. 25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients. BMC Nephrol., 2011, 12(1), 24.
[http://dx.doi.org/10.1186/1471-2369-12-24] [PMID: 21600051]
[58]
Kim, S.H.; Baek, M.S.; Yoon, D.S.; Park, J.S.; Yoon, B.W.; Oh, B.S.; Park, J.; Kim, H.J. Vitamin D inhibits expression and activity of matrix metalloproteinase in human lung fibroblasts (HFL-1) cells. Tuberc. Respir. Dis. (Seoul), 2014, 77(2), 73-80.
[http://dx.doi.org/10.4046/trd.2014.77.2.73] [PMID: 25237378]
[59]
Bakdash, G.; van Capel, T.M.; Mason, L.M.; Kapsenberg, M.L.; de Jong, E.C. Vitamin D3 metabolite calcidiol primes human dendritic cells to promote the development of immunomodulatory IL-10-producing T cells. Vaccine, 2014, 32(47), 6294-6302.
[http://dx.doi.org/10.1016/j.vaccine.2014.08.075] [PMID: 25236584]
[60]
Koenen, H.J.; Smeets, R.L.; Vink, P.M.; van Rijssen, E.; Boots, A.M.; Joosten, I. Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood, 2008, 112(6), 2340-2352.
[http://dx.doi.org/10.1182/blood-2008-01-133967] [PMID: 18617638]
[61]
Oida, T.; Xu, L.; Weiner, H.L.; Kitani, A.; Strober, W. TGF-β-mediated suppression by CD4+CD25+ T cells is facilitated by CTLA-4 signaling. J. Immunol., 2006, 177(4), 2331-2339.
[http://dx.doi.org/10.4049/jimmunol.177.4.2331] [PMID: 16887994]
[62]
Mohammadi, M.; Gozashti, M.H.; Aghadavood, M.; Mehdizadeh, M.R.; Hayatbakhsh, M.M. Clinical Significance of Serum IL-6 and TNF-α Levels in Patients with Metabolic Syndrome. Rep. Biochem. Mol. Biol., 2017, 6(1), 74-79.
[PMID: 29090232]
[63]
Ysmail-Dahlouk, L.; Nouari, W.; Aribi, M. 1,25-dihydroxyvitamin D3 down-modulates the production of proinflammatory cytokines and nitric oxide and enhances the phosphorylation of monocyte-expressed STAT6 at the recent-onset type 1 diabetes. Immunol. Lett., 2016, 179, 122-130.
[http://dx.doi.org/10.1016/j.imlet.2016.10.002] [PMID: 27717877]
[64]
Urry, Z.; Chambers, E.S.; Xystrakis, E.; Dimeloe, S.; Richards, D.F.; Gabryšová, L.; Christensen, J.; Gupta, A.; Saglani, S.; Bush, A.; O’Garra, A.; Brown, Z.; Hawrylowicz, C.M. The role of 1α,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+ and IL-10+ CD4+ T cells. Eur. J. Immunol., 2012, 42(10), 2697-2708.
[http://dx.doi.org/10.1002/eji.201242370] [PMID: 22903229]

Rights & Permissions Print Cite
Article Metrics
20
1
© 2024 Bentham Science Publishers | Privacy Policy