1,25 Dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNγ axis leading to Th1 response in experimental allergic encephalomyelitis

Journal of Neuroscience Research

Volumn 83, Issue 7, 2006, Pages 1299-1309

  Muthian, Gladson ^a   Raikwar, Himanshu P ^a   Rajasingh, Johnson ^a   Bright, John J ^a,b,c  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c METHODIST RESEARCH INSTITUTE   (United States)

Author keywords

Cytokine signaling; EAE MS; Immunomodulation; Inflammation; Th1 response; Vitamin D

Indexed keywords

CALCITRIOL; GAMMA INTERFERON; INTERLEUKIN 12; JANUS KINASE; JANUS KINASE 2; STAT PROTEIN; STAT1 PROTEIN; STAT3 PROTEIN; STAT4 PROTEIN; VITAMIN D; VITAMIN D RECEPTOR;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL STIMULATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG EFFECT; ENZYME INHIBITION; FEMALE; IMMUNOMODULATION; INFLAMMATION; MICROGLIA; MOUSE; MULTIPLE SCLEROSIS; NEUROMODULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SPLEEN CELL; T LYMPHOCYTE ACTIVATION; TH1 CELL;

ANIMALS; CALCITRIOL; CELLS, CULTURED; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; IMMUNITY, CELLULAR; INTERFERON TYPE II; INTERLEUKIN-12; JANUS KINASE 2; LYMPHOCYTE ACTIVATION; MICE; MICE, INBRED C57BL; MICROGLIA; PHOSPHORYLATION; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS; SIGNAL TRANSDUCTION; STAT1 TRANSCRIPTION FACTOR; TH1 CELLS;

EID: 33646339134     PISSN: 03604012     EISSN: 10974547     Source Type: Journal    
DOI: 10.1002/jnr.20826     Document Type: Article

References (84)

1. Bacon CM, Petricoin EM, Ortaldo JR, Rees RC, Lamer AC, Johnston JA, O'Shea JJ. 1995. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. Proc Natl Acad Sci USA 92:7307-7311.
2. Bass S, Prufer K, Ittlel ME, Kuchler-Bopp S, Labourdette G, Sarlieve LL, Brachet P. 2000. Rat oligodendrocytes express the vitamin D(3) receptor and respond to 1,25-dihydroxyvitamin D3. Glia 1:59-68.
3. Balashov KE, Smith DR, Khoury SJ, Hafler DA, Weiner HL. 1997. Increased interleukin-12 production in progressive multiple sclerosis: induction by activated CD+ T cells via CD40 ligand. Proc Natl Acad Sci USA 94:599-603.
4. Becher B, Blain M, Antel JP. 2000. CD40 engagement stimulates IL-12 p70 production by human microglial cells: basis for Th1 polarization in the CNS. J Neuroimmunol 102:44-50.
5. Becher B, Durell BG, Noelle RJ. 2003. IL-23 produced by CNS resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis. J Clin Invest 112:1186-1191.
6. Benveniste EN. 1997. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med 75:165-173.
7. Bertagonolli MM, Lin BY, Young D, Herrmann SH. 1992. IL-12 augments antigen-dependent proliferation of activated T Lymphocytes. J Immunol 149:3778-3783.
8. Bettelli E, Nicholson. 2000. The role of cytokines in experimental autoimmune encephalomyelitis. Arch Immunol Ther Exp 48:389-398.
9. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK. 2004. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 200:79-87.
10. Bettelli E, Kuchroo VK. 2005. IL-12- and IL-23-induced T helper cell subsets: birds of the same feather flock together. J Exp Med 201:169-171.
11. Bhalla AK, Amento EP, Serog B, Glimcher LH. 1984. 1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol 133:1748-1754.
12. Branisteanu DD, Mathieu C, Bouillon R. 1997. Synergism between sirolimus and 1,25-dihydroxy vitamin D3 in vitro and in vivo. J Neuro Immunol 79:138-147.
13. Bright JJ, Sriram S. 1997. TGF-beta inhibits IL-12-induced tyrosine phosphorylation and activation of JAK1 and STAT5 in lymphocytes. J Immunol 159:175-183.
14. Bright JJ, Musuro BF, Du C, Sriram S. 1998a. Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic encephalomyelitis. J Neuroimmunol 82:22-30.
15. Bright JJ, Du C, Coon M, Sriram S, Klaus SJ. 1998b. Prevention of experimental allergic encephalomyelitis via inhibition of IL-12 signaling and IL-12-mediated Th1 differentiation: an effect of the novel anti-inflammatory drug lisofylline. J Immunol 161:7015-7022.
16. Bright JJ, Du C, Sriram S. 1999. Tyrophostin B42 inhibits IL-12 induced tyrosine phosphorylation and activation of Janus kinase-2 and prevents experimental allergic encephalomyelitis. J Immunol 162:6255-6262.
17. Bright JJ, Sriram S. 2001. Immunotherapy of inflammatory demyelinating diseases of the central nervous system. Immunol Res 23:245-52.
18. Cantorna MT, Woodward WD, Hayes CE, DeLuca HF. 1998. 1,25-Dihydroxy D3 is a positive regulator for the two anti-encephalitogenic cytokines TGFβ and IL-4. Structure-function relationship in the vitamin D endocrine system. Endocr Rev 16:200-257.
19. Cantorna MT, Humpal-Winter J, DeLuca HF. 1999. Dietary calcium is a major factor in 1,25 dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice. J Nutr 129:1966-1971.
20. Clegg A, Bryant J. 2001. Immunomodulatory drugs for multiple sclerosis: A systemic review of clinical and cost effectiveness. Expert Opin Pharm Ther 2:623-639.
21. Comabella M, Balashov K, Issazdeh S, Smith D, Weiner HL, Khoury SJ. 1998. Elevated interleukin 12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy. J Clin Invest 102:671-678.
22. Constantinescu CS, Hilliard B, Wysocka M, Ventura ES, Bhopale MK, Trinchieri G, Rostami AM. 1999. IL-12 reverses the suppressive effect of the CD40 ligand blockade on experimental autoimmune encephalomyelitis (EAE). J Neurol Sci 171:60-64.
23. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelin RA, Sedgwick JD. 1997. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:706-708.
24. D'Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, DiLucia P, Lang R, Singaglia F, Panina-Bordignon P. 1998. Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3 involvement of NF-kappa B downregulation in transcriptional repression of the P40 gene. J Clin Invest 101:252-262.
25. Darnell JE, Kerr IM, Stark GR. 1994. JAK-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415-1421.
26. Dean G. 1994. How many people in the world have MS? Neuroepidemiology 13:1-7.
27. DeLuca HF, Cantorna MT. 2001. Vitamin D: its role and uses in immunology. FASEB J 15:2579-2585.
28. Donoghue S, Greenless C. 2000. Drugs in development for the treatment of multiple sclerosis: antigen nonspecific therapies, an update. Expert Opin Invest Drugs 9:167-171.
29. Drulovic J, Mostraica-Stojkovic M, Levic Z, Mesaros S, Stojavljevic N, Popadi D, Pravica V. 1998. Serum interleukin 12 levels in patient with multiple sclerosis. Neurosci Lett 251:129-132.
30. Du C, Bright JJ, Sriram S. 2001. Inhibition of CD40 signaling pathway by Tyrophostin A1 reduces secretion of IL-12 in macrophage, Th1 development and experimental allergic encephalomyelitis in SJL/J mice. J Neuroimmunol 114:69-79.
31. Ebers GC, Sadovnick AD, 1993. The geographic distribution of multiple sclerosis: a review. Neuroepidemiology 12:1-5.
32. Fassbender K, Ragoschke A, Rossol S, Schwartz A, Mielke O, Paulig A, Hennerici M. 1998. Increased release of interleukin-12 p40 in MS: association with intracerebral inflammation. Neurology 51:753-758.
33. Freedman DM, Dosemeci M, Alavanja MC. 2000. Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case control study based on death certificates. Occup Environ Med 57:418-421.
34. Garicion E, Sindji L, Nataf S, Brachet P, Darcy F, Montero-Menei CN. 2003. Treatment of experimental autoimmune encephalomyelitis in rat by 1,25 dihydroxyvitamin D3 leads to early effects within the central nervous system. Acta Neuropathol 105:438-448.
35. Gately MK, Desai BB, Wolitzky AG, Quinn PM, Dwyer CM, Podlaski FJ, Familletti PC, Shingaglia F, Chizonnite R, Gubler U. 1991. Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J Immunol 147:874-882.
36. Gold R, Hartung HP, Toyka KV. 2000. Animals model for auto immune demyelinating disorders of the nervous system. Mol Med Today 6:88-91.
37. Gran B, Zhang GX, Yu S, Li J, Chen XH, Ventura ES, Kamoun M, Rostami A. 2002. IL-12p35 deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J Immunol 169:7104-7110.
38. Heesen C, Sieverding F, Schoser BG, Hadgi B, Kunze K. 1999. IL-12 is detectable in sera of patients with multiple sclerosis: association with chronic progressive disease course? Eur J Neurol 6:591-596.
39. Heremans H, Dillen C, Groenen M, Matthys P, Billiau A. 1999. Role of endogenous interleukin-12 (IL-12) in induced and spontaneous relapses of experimental autoimmune encephalomyelitis in mice. Eur Cytokine Netw 10:171-180.
40. Holick MF, Smith E, Pincus S. 1987. Skin as the state of vitamin D synthesis and target tissue for 1,25-dihydroxy vitamin D3. Arch Dermatol 123:1677-1683.
41. Jacobson NG, Szabo SJ, Weber Nordt RM, Zhong Z, Schreiber RD, Darnell Jr JE, Murphy KM 1995. Interleukin-12 signaling in T helper type 1 (Th1) cells involve tyrosine phosphorylation of signal transducer and activator of transcription Stat3 and Stat4. J Exp Med 181:1755-1762.
42. Kamiya S, Owaki T, Morishima N, Fukai F, Mizuguchi J, Yoshimoto T. 2004. An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4+ T cells. J Immunol 173:3871-3877.
43. Karp CL. 1999. Interleukin-12: amiss in MS. Ann Neurol 45:689-692.
44. Kile BT, Nicola NA, Alexander WS. 2001. Negative regulators of cytokine signaling. Int J Hematol 73:292-298.
45. Krebs DL, Hilton DJ. 2001. SOCS proteins: negative regulators of cytokine signaling. Stem Cells 19:378-387.
46. Kreutz M, Andreesen R, Krause SW, Szabo A, Ritz E, Reichel H. 1993. 1,25-Dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages. Blood 82:1300-1307.
47. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. 2005. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233-240.
48. Leonard JP, Waldburger KE, Goldman SJ. 1995. Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. J Exp Med 181:381-386.
49. Li J, Gran B, Zhang GX, Ventura ES, Siglienti I, Rostami A, Kamoun M. 2003. Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia. J Neurol Sci 215:95-103.
50. Lighvani AA, Frucht DM, Jankovic D, Yamane H, Aliberti J, Hissong BD, Nguyen BV, Gadina M, Sher A, Paul WE, O'Shea JJ. 2001. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc Natl Acad Sci USA 98:15137-15142.
51. Lovett-Racke AE, Rocchini AE, Choy J, Northrop SC, Hussain RZ, Ratts RB, Sikder D, Racke MK. 2004. Silencing T-bet defines a critical role in the differentiation of auto reactive T lymphocytes. Immunity 21:719-731.
52. Lucas S, Ghilardi N, Li J, de Sauvage FJ. 2003. IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc Natl Acad Sci USA 100:15047-15052.
53. Lyakh LA, Sanford M, Chekol S, Young HA, Roberts AB. 2005. TGF-beta and vitamin D3 utilize distinct pathways to suppress IL-12 production and modulate rapid differentiation of human monocytes into CD83+ dendritic cells. J Immunol 174:2061-2070.
54. Ma X, Neurath M, Gri G, Trinchieri G. 1997. Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene promoter. J Biol Chem 272:10389-10395.
55. Mathieu C, Adorini L. 2002. The coming of age of 1,25-dihydroxyvitamin D (3) analogs as immunomodulatory agents. Trend Mol Med 8:174-179.
56. Mattner F, Smiroldo S, Galbiati F, Muller M, Di Lucia P, Poliant PL, Martino G, Panina-Bordignon P, Adorini L. 2000. Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non hypercalcemic analogue of 1,25-dihydroxyvitamin D3. Eur J Immunol 30:498-508.
57. Meehan TF, DeLuca HF. 2002. The vitamin D receptor is necessary for 1 alpha,25-dihydroxy vitamin D (3) to suppress experimental autoimmune encephalomyelitis in mice. Arch Biochem Biophys 408:200-204.
58. Mullen AC, High FA, Hutchins AS, Lee HW, Villarino AV, Livingston DM, Kung AL, Cereb N, Yao TP, Yang SY, Reiner SL. 2001. Role of T-bet in commitment of Th1 cells before IL-12-dependent selection. Science 292:1907-1910.
59. Murphy TL, Cleveland MG, Kulezsza P, Magram J, Murphy KM. 1995. Regulation of interleukin 12-p40 expression through and NF-κβ half-site. Mol Cell Biol 15:5258-5267.
60. Muthian G, Bright J. 2004. Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocytes. J Clin Immunol 24:538-551.
61. Natarajan C, Bright JJ. 2002a. Peroxisome proliferators-activated receptor gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation. Genes Immun 3:59-70.
62. Natarajan C, Bright JJ. 2002b. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK STAT pathway in T cells and differentiation of neural antigen specific Th1 cells. J Immunol 169:6506-6513.
63. Nath N, Giri S, Prasad R, Salem ML, Singh AK, Singh I. 2005. 5-Amino-imidazole-4 carboxamide ribonucleoside: a novel immunomodulator with therapeutic efficacy in experimental autoimmune encephalomyelitis. J Immunol 175:566-574.
64. Nicoletti F, Patti C, Cocuzza C, Zaccone P, Nicoletti A, Di Marco R, Reggio A. 1996. Elevated serum levels of interleukin-12 in chronic progressive multiple sclerosis. J Neuroimmunol 70:87-90.
65. Nguyen T, Wang R, Russell JH. 2000. IL-12 enhances IL-12 function by inducing CD25 expression through a p38 mitogen activated protein kinase pathway. Eur J Immunol 30:1445-1452.
66. O'Connor KC, Bar-Or A, Haffler DA. 2001. The neuroimmunology of multiple sclerosis: possible roles of T and B lymphocytes in immunopathogenesis. J Clin Immunol 21:81-92.
67. Overbergh L, Decallonne B, Valckx D, Verstuyf A, Depovere J, Laureys J, Rutgeerts O, Saint-Arnaud R, Bouillon R, Mathieu C. 2000. Identification and immune regulation of 25-hydroxy vitamin D1 alpha-hydroxylase in murine macrophages. Clin Exp Immunol 120:139-146.
68. Owens T, Sriram S. 1995. The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis. Neurol Clin 13:51-73.
69. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, German D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW. 2002. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168:5699-5708.
70. Reichel H, Koeffler HP, Tobler A, Norman AW. 1987. 1 alpha, 25-Dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. Proc Natl Acad Sci USA 84:3385-3389.
71. Smith T, Hewson AK, Kingsley CI, Leonard JP, Cuzner ML. 1997. Interleukin-12 induces relapses in experimental allergic encephalomyelitis in the Lewis rat. Am J Pathol 150:1909-1917.
72. Starr R, Hilton DJ. 1999. Negative regulation of the JAK/STAT pathway. Bioessays 21:47-52.
73. Steinman L, Martin M, Bernard C, Conlon P, Oksenberg JR. 2002. Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy. Annu Rev Neurosci 25:491-505.
74. Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH. 2002. Distinct effects of T-bet in Th1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295:338-342.
75. Trembleau ST, Germann M, Gately K, Adorini L. 1995. The role of IL-12 in the induction of organ-specific autoimmune diseases. Immunol Today 16:383-386.
76. Trinchieri G. 1995. Interleukin 12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 13:251-276.
77. Trinchieri G. 2003. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133-146.
78. VanAmerongen BM, Dijkstra CD, Lips P, Polman CH. 2004. Multiple sclerosis and vitamin D an update. Eur J Clin Nutr 58:1095-1109.
79. van Etten E, Branisteanu DD, Verstuyf A, Waer M, Bouillon R, Mathieu C. 2000. Analogs of 1,25 dihydroxy vitamin D3 as dose reducing agents for classical immunosuppressants. Transplantation 69:1932-1942.
80. Walker WS, Gatewood J, Olivas E, Askew D, Havenith CE. 1995. Mouse microglial cell lines differing in constitutive and interferon-γ inducible antigen-presenting activities for naive and memory CD4+ and CD8+ T cells. J Neuroimmunol 63:163-174.
81. Wang IM, Contursi C, Masumi A, Ma X, Trinchieri G, Ozato K. 2000. An IFN-gamma-inducible transcription factor, IFN consensus sequence binding protein (ICSBP), stimulates IL-12 p40 expression in macrophages. J Immunol 165:271-279.
82. Wingerchuk DM, Lucchinetti CF, Noseworthy JH. 2001. Multiple sclerosis: current pathophysiological concepts. Lab Invest 81:263-281.
83. Yanagida T, Kato T, Igarashi O, Inoue T, Nariuchi H. 1994. Second signal activity of IL-12 on the proliferation and IL-2 R expression of T helper cell-1 clone. J Immunol 152:4919-4928.
84. Zhang G, Ghosh S. 2000. Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll like receptors. J Endotoxin Res 6:453-457.