2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 51, 2012, Pages 21034-21039

  Duncan, Gordon S ^a   Brenner, Dirk ^a,b   Tusche, Michael W ^a   Brus̈tle, Anne ^a   Knobbe, Christiane B ^a,e   Elia, Andrew J ^a   Mock, Thomas ^c   Bray, Mark R ^a   Krammer, Peter H ^c   Mak, Tak W ^a,d  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d UNIVERSITY OF TORONTO   (Canada)

^e HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

Autoimmunity; Calcium signaling

Indexed keywords

2 METHOXYESTRADIOL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 17; NUCLEAR FACTOR OF ACTIVATED T CELLS C1; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR NFAT; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATTENUATION; B LYMPHOCYTE ACTIVATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; IN VITRO STUDY; INHIBITION KINETICS; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION;

ANIMALS; AUTOIMMUNITY; CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; ESTRADIOL; HUMANS; LYMPHOCYTE ACTIVATION; LYMPHOCYTES; MICE; MICE, INBRED C57BL; MULTIPLE SCLEROSIS; NF-KAPPA B; NFATC TRANSCRIPTION FACTORS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR AP-1; TUBULIN MODULATORS;

ANIMALIA; RODENTIA;

EID: 84871370448     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1215558110     Document Type: Article

References (53)

1. Jadidi-Niaragh F, Mirshafiey A (2011) Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol 74(1):1-13.
2. Frohman EM, Racke MK, Raine CS (2006) Multiple sclerosis - the plaque and its pathogenesis. N Engl J Med 354(9):942-955.
3. Stromnes IM, Goverman JM (2006) Active induction of experimental allergic encephalomyelitis. Nat Protoc 1(4):1810-1819.
4. Batoulis H, Recks MS, Addicks K, Kuerten S (2011) Experimental autoimmune encephalomyelitis - achievements and prospective advances. APMIS 119(12):819-830.
5. Pollinger B (2012) IL-17 producing T cells in mouse models of multiple sclerosis and rheumatoid arthritis. J Mol Med 90(6):613-624.
6. Zepp J, Wu L, Li X (2011) IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease. Trends Immunol 32(5):232-239.
7. Matusevicius D, et al. (1999) Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler 5(2):101-104.
8. Durelli L, et al. (2009) T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta. Ann Neurol 65(5):499-509.
9. Gonzalez-García I, et al. (2009) IL-17 signaling-independent central nervous system autoimmunity is negatively regulated by TGF-beta. J Immunol 182(5):2665-2671.
10. Hu Y, et al. (2010) IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 184(8):4307-4316.
11. Komiyama Y, et al. (2006) IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 177(1):566-573.
12. Park H, et al. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6(11):1133-1141.
13. LaVallee TM, et al. (2002) 2-Methoxyestradiol inhibits proliferation and induces apoptosis independently of estrogen receptors alpha and beta. Cancer Res 62(13):3691-3697.
14. Pribluda VS, et al. (2000) 2-Methoxyestradiol: An endogenous antiangiogenic and antiproliferative drug candidate. Cancer Metastasis Rev 19(1-2):173-179.
15. Sutherland TE, et al. (2007) 2-Methoxyestradiol - a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents. Drug Discov Today 12(13-14):577-584.
16. Gökmen-Polar Y, et al. (2005) beta-Tubulin mutations are associated with resistance to 2-methoxyestradiol in MDA-MB-435 cancer cells. Cancer Res 65(20):9406-9414.
17. Mabjeesh NJ, et al. (2003) 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3(4):363-375.
18. Escuin D, Kline ER, Giannakakou P (2005) Both microtubule-stabilizing and microtubule-destabilizing drugs inhibit hypoxia-inducible factor-1alpha accumulation and activity by disrupting microtubule function. Cancer Res 65(19):9021-9028.
19. Josefsson E, Tarkowski A (1997) Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol. Arthritis Rheum 40(1):154-163.
20. Plum SM, et al. (2009) Disease modifying and antiangiogenic activity of 2-methoxyestradiol in a murine model of rheumatoid arthritis. BMC Musculoskelet Disord 10:46.
21. Issekutz AC, Sapru K (2008) Modulation of adjuvant arthritis in the rat by 2-methoxyestradiol: An effect independent of an anti-angiogenic action. Int Immunopharmacol 8(5):708-716.
22. Berg D, Sonsalla R, Kuss E (1983) Concentrations of 2-methoxyoestrogens in human serum measured by a heterologous immunoassay with an 125I-labelled ligand. Acta Endocrinol (Copenh) 103(2):282-288.
23. Huh JI, et al. (2007) 2-methoxyestradiol induces mammary gland differentiation through amphiregulin-epithelial growth factor receptor-mediated signaling: Molecular distinctions from the mammary gland of pregnant mice. Endocrinology 148(3):1266-1277.
24. Ostensen M, Villiger PM (2007) The remission of rheumatoid arthritis during pregnancy. Semin Immunopathol 29(2):185-191.
25. Offner H, Polanczyk M (2006) A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. Ann N Y Acad Sci 1089:343-372.
26. Lubberts E (2010) Th17 cytokines and arthritis. Semin Immunopathol 32(1):43-53.
27. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485-517.
28. Matei D, et al. (2009) Activity of 2 methoxyestradiol (Panzem NCD) in advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: A Hoosier Oncology Group trial. Gynecol Oncol 115(1):90-96.
29. Becher B, Segal BM (2011) T(H)17 cytokines in autoimmune neuro-inflammation. Curr Opin Immunol 23(6):707-712.
30. Kurata H, Lee HJ, O'Garra A, Arai N (1999) Ectopic expression of activated Stat6 induces the expression of Th2-specific cytokines and transcription factors in developing Th1 cells. Immunity 11(6):677-688.
31. Miethke T, et al. (1992) T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: Critical role of tumor necrosis factor. J Exp Med 175(1):91-98.
32. Blasko E, et al. (2009) Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis. J Neuroimmunol 214(1-2):67-77.
33. Bodhankar S, Offner H (2011) Gpr30 forms an integral part of E2-protective pathway in experimental autoimmune encephalomyelitis. Immunol Endocr Metab Agents Med Chem 11(4):262-274.
34. Yates MA, Li Y, Chlebeck PJ, Offner H (2010) GPR30, but not estrogen receptor-alpha, is crucial in the treatment of experimental autoimmune encephalomyelitis by oral ethinyl estradiol. BMC Immunol 11:20.
35. Oh-hora M, Rao A (2008) Calcium signaling in lymphocytes. Curr Opin Immunol 20(3):250-258.
36. Zou H, et al. (2006) 2-methoxyestradiol, an endogenous mammalian metabolite, radiosensitizes colon carcinoma cells through c-Jun NH2-terminal kinase activation. Clin Cancer Res 12(21):6532-6539.
37. Lorin S, et al. (2009) c-Jun NH2-terminal kinase activation is essential for DRAM-dependent induction of autophagy and apoptosis in 2-methoxyestradiol- treated Ewing sarcoma cells. Cancer Res 69(17):6924-6931.
38. D'Amato RJ, Lin CM, Flynn E, Folkman J, Hamel E (1994) 2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site. Proc Natl Acad Sci USA 91(9):3964-3968.
39. Zacharia LC, et al. (2003) Methoxyestradiols mediate the antimitogenic effects of 17beta-estradiol: Direct evidence from catechol-O-methyltransferase- knockout mice. Circulation 108(24):2974-2978.
40. Shand FH, et al. (2011) In vitro and in vivo evidence for anti-inflammatory properties of 2-methoxyestradiol. J Pharmacol Exp Ther 336(3):962-972.
41. Verenich S, Gerk PM (2010) Therapeutic promises of 2-methoxyestradiol and its drug disposition challenges. Mol Pharm 7(6):2030-2039.
42. LaVallee TM, et al. (2008) Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198. Mol Cancer Ther 7(6):1472-1482.
43. Tevaarwerk AJ, et al. (2009) Phase I trial of 2-methoxyestradiol NanoCrystal dispersion in advanced solid malignancies. Clin Cancer Res 15(4):1460-1465.
44. Kulke MH, et al. (2011) A prospective phase II study of 2-methoxyestradiol administered in combination with bevacizumab in patients with metastatic carcinoid tumors. Cancer Chemother Pharmacol 68(2):293-300.
45. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22(3):659-661.
46. Hogan PG, Chen L, Nardone J, Rao A (2003) Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 17(18):2205-2232.
47. Aussel C, Marhaba R, Pelassy C, Breittmayer JP (1996) Submicromolar La3+ concentrations block the calcium release-activated channel, and impair CD69 and CD25 expression in CD3- or thapsigargin-activated Jurkat cells. Biochem J 313(Pt 3):909-913.
48. Taylor-Fishwick DA, Siegel JN (1995) Raf-1 provides a dominant but not exclusive signal for the induction of CD69 expression on T cells. Eur J Immunol 25(12):3215-3221.
49. Castellanos MdelC, López-Giral S, López-Cabrera M, de Landázuri MO (2002) Multiple cis-acting elements regulate the expression of the early T cell activation antigen CD69. Eur J Immunol 32(11):3108-3117.
50. Macián F, López-Rodríguez C, Rao A (2001) Partners in transcription: NFAT and AP-1. Oncogene 20(19):2476-2489.
51. Tsytsykova AV, Goldfeld AE (2000) Nuclear factor of activated T cells transcription factor NFATp controls superantigen-induced lethal shock. J Exp Med 192(4):581-586.
52. Kumar AP, Garcia GE, Orsborn J, Levin VA, Slaga TJ (2003) 2-Methoxyestradiol interferes with NF kappa B transcriptional activity in primitive neuroectodermal brain tumors: Implications for management. Carcinogenesis 24(2):209-216.
53. Brahn E, et al. (2008) An angiogenesis inhibitor, 2-methoxyestradiol, involutes rat collagen-induced arthritis and suppresses gene expression of synovial vascular endothelial growth factor and basic fibroblast growth factor. J Rheumatol 35(11):2119-2128.