HE3286, an orally bioavailable synthetic analogue of an active DHEA metabolite suppresses spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse

European Journal of Pharmacology

Volumn 658, Issue 2-3, 2011, Pages 257-262

  Kosiewicz, Michele M ^a   Auci, Dominick L ^b   Fagone, Paolo ^c   Mangano, Katia ^c   Caponnetto, Salvatore ^c   Tucker, Colleen F ^a   Azeem, Nabeel ^a   White, Steven K ^b   Frincke, James M ^b   Reading, Christopher L ^b   Nicoletti, Ferdinando ^c  

^a University of Louisville School of Medicine   (United States)

^b Harbor Biosciences   (United States)

^c UNIVERSITY OF CATANIA   (Italy)

Author keywords

Androstene; Diabetes; IL 17; NOD; Steroid

Indexed keywords

17 ALPHA ETHYNYL 5 ANDROSTENE 3 BETA,7 BETA,17 BETA TRIOL; ANTIDIABETIC AGENT; HE 3286; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; AUTOIMMUNE DISEASE; CLINICAL EVALUATION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG MECHANISM; DRUG STRUCTURE; FEMALE; HISTOPATHOLOGY; IMMUNOMODULATION; INSULIN DEPENDENT DIABETES MELLITUS; INSULITIS; LYMPHOID ORGAN; MOUSE; NONHUMAN; NONOBESE DIABETIC MOUSE; PHENOTYPE; PRIORITY JOURNAL; TH1 CELL; TH17 CELL;

ADMINISTRATION, ORAL; ANIMALS; ANTIGENS, CD4; BIOLOGICAL AVAILABILITY; DEHYDROEPIANDROSTERONE; DIABETES MELLITUS, TYPE 1; FEMALE; INFLAMMATION; ISLETS OF LANGERHANS; MICE; MICE, INBRED NOD; SPLEEN; T-LYMPHOCYTES, REGULATORY;

EID: 79953791858     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2011.02.016     Document Type: Article

References (44)

1. Akirav, E., Kushner, J.A., Herold, K.C., 2008. Beta-cell mass and type 1 diabetes: going, going, gone? Diabetes 57, 2883-2888.
2. Anderson, M.S., Bluestone, J.A., 2005. The NOD mouse: a model of immune dysregulation. Annu. Rev. Immunol. 23, 447-485.
3. Aoki, C.A., Borchers, A.T., Ridgway, W.M., Keen, C.L., Ansari, A.A., Gershwin, M.E., 2005. NOD mice and autoimmunity. Autoimmun. Rev. 4, 373-379.
4. Atkinson, M.A., Maclaren, N.K., 1994. The pathogenesis of insulin-dependent diabetes mellitus. N. Engl. J. Med. 331, 1428-1436.
5. Auci, D., Kaler, L., Subramanian, S., Huang, Y., Frincke, J., Reading, C., Offner, H., 2007. A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the mouse: androstene hormones as regulators of regulatory T cells. Ann. NY Acad. Sci. 1110, 630-640.
6. Auci, D.L., Reading, C.L., Frincke, J.M., 2009. 7-Hydroxy androstene steroids and a novel synthetic analogue with reduced side effects as a potential agent to treat autoimmune diseases. Autoimmun. Rev. 8, 369-372.
7. Auci, D.L., Mangano, K., Destiche, D., White, S.K., Huang, Y., Boyle, D., Frincke, J., Reading, C.L., Nicoletti, F., 2010. Oral treatment with HE3286 ameliorates disease in rodent models of rheumatoid arthritis. Int. J. Mol. Med. 25, 625-633.
8. Awasthi, A., Murugaiyan, G., Kuchroo, V.K., 2008. Interplay between effector Th17 and regulatory T cells. J. Clin. Immunol. 28, 660-670.
9. Bending, D., De La Pena, H., Veldhoen, M., Phillips, J.M., Uyttenhove, C., Stockinger, B., Cooke, A., 2009. Highly purified Th17 cells from BDC2.5NOD mice convert into Th1- like cells in NOD/SCID recipient mice. J. Clin. Invest. (Feb 2, Electronic publication ahead of print).
10. Bollyky, J., Sanda, S., Greenbaum, C.J., 2008. Type 1 diabetes mellitus: primary, secondary, and tertiary prevention. Mt. Sinai J. Med. 75, 385-397.
11. Bresson, D., von Herrath, M., 2007. Moving towards efficient therapies in type 1 diabetes: to combine or not to combine? Autoimmun. Rev. 6, 315-322. (Pubitemid 46507996)
12. Cernea, S., Pozzilli, P., 2008. New potential treatments for protection of pancreatic B-cell function in Type 1 diabetes. Diabet. Med. 25, 1259-1267.
13. Cohn, M., 2008. What roles do regulatory T cells play in the control of the adaptive immune response? Int. Immunol. 20, 1107-1118.
14. Debray-Sachs, M., Carnaud, C., Boitard, C., Cohen, H., Gresser, I., Bedossa, P., Bach, J.F., 1991. Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma. J. Autoimmun. 4, 237-248.
15. Dillon, J.S., 2005. Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: their role in inflammatory, allergic and immunological disorders. Curr. Drug Targets Inflamm. Allergy 4, 377-385.
16. Drage, M., Zaccone, P., Phillips, J.M., Nicoletti, F., Dawson, J., Andrew Bradley, J., Cooke, A., 2002. Nondepleting anti-CD4 and soluble interleukin-1 receptor prevent autoimmune destruction of syngeneic islet grafts in diabetic NOD mice. Transplantation 74, 611-619.
17. Emamaullee, J.A., Davis, J., Merani, S., Toso, C., Elliott, J.F., Thiesen, A., Shapiro, A.M., 2009. Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes 58, 1302-1311.
18. Feuerer, M., Jiang, W., Holler, P.D., Satpathy, A., Campbell, C., Bogue, M., Mathis, D., Benoist, C., 2007. Enhanced thymic selection of FoxP3+ regulatory T cells in the NOD mouse model of autoimmune diabetes. Proc. Natl Acad. Sci. USA 104, 18181-18186.
19. Giarratana, N., Penna, G., Adorini, L., 2007. Animal models of spontaneous autoimmune disease: type 1 diabetes in the nonobese diabetic mouse. Meth. Mol. Biol. 380, 285-311.
20. Harrison, L.C., Honeyman, M.C., Morahan, G., Wentworth, J.M., Elkassaby, S., Colman, P.G., Fourlanos, S., 2008. Type 1 diabetes: lessons for other autoimmune diseases? J. Autoimmun. 31, 306-310.
21. Hung, J.T., Liao, J.H., Lin, Y.C., Chang, H.Y., Wu, S.F., Chang, T.H., Kung, J.T., Hsieh, S.L., McDevitt, H., Sytwu, H.K., 2005. Immunopathogenic role of TH1 cells in autoimmune diabetes: evidence from a T1 and T2 doubly transgenic non-obese diabetic mouse model. J. Autoimmun. 25, 181-192. (Pubitemid 41654462)
22. Ivanov, S., Linden, A., 2009. Interleukin-17 as a drug target in human disease. Trends Pharmacol. Sci. 30, 95-103.
23. Jain, R., Tartar, D.M., Gregg, R.K., Divekar, R.D., Bell, J.J., Lee, H.H., Yu, P., Ellis, J.S., Hoeman, C.M., Franklin, C.L., Zaghouani, H., 2008. Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. J. Exp. Med. 205, 207-218.
24. Kelchtermans, H., De Klerck, B., Mitera, T., Van Balen, M., Bullens, D., Billiau, A., Leclercq, G., Matthys, P., 2005. Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma. Arthritis Res. Ther. 7 (2), R402-R415.
25. Kroboth, P.D., Salek, F.S., Pittenger, A.L., Fabian, T.J., Frye, R.F., 1999. DHEA and DHEA-S: a review. J. Clin. Pharmacol. 39, 327-348.
26. Lebovitz, H.E., 2010. Adjunct therapy for type 1 diabetes mellitus. Nat. Rev. Endocrinol. 6, 326-334.
27. Lu, M., Patsouris, D., Li, P., Flores-Riveros, J., Frincke, J.M., Watkins, S., Schenk, S., Olefsky, J.M., 2010. A new antidiabetic compound attenuates inflammation and insulin resistance in Zucker diabetic fatty rats. Am. J. Physiol. Endocrinol. Metab. 298 (5), E1036-E1048 May.
28. Martin-Orozco, N., Chung, Y., Chang, S.H., Wang, Y.H., Dong, C., 2009. Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells. Eur. J. Immunol. 39, 216-224.
29. Mellanby, R.J., Thomas, D., Phillips, J.M., Cooke, A., 2007. Diabetes in non-obese diabetic mice is not associated with quantitative changes in CD4+ CD25+ Foxp3+ regulatory T cells. Immunology 121, 15-28. (Pubitemid 46537670)
30. Mor, A., Kloog, Y., Keren, G., George, J., 2009. Ras inhibition increases the frequency and function of regulatory T cells and attenuates type-1 diabetes in non-obese diabetic mice. Eur. J. Pharmacol. 616 (1-3), 301-305.
31. Nicoletti, F., Di Marco, R., Barcellini, W., Magro, G., Schorlemmer, H.U., Kurrle, R., Lunetta, M., Grasso, S., Zaccone, P., Meroni, P., 1994. Protection from experimental autoimmune diabetes in the non-obese diabetic mouse with soluble interleukin-1 receptor. Eur. J. Immunol. 24, 1843-1847.
32. Nicoletti, F., Zaccone, P., Di Marco, R., Di Mauro, M., Magro, G., Grasso, S., Mughini, L., Meroni, P., Garotta, G., 1996. The effects of a nonimmunogenic form of murine soluble interferon-gamma receptor on the development of autoimmune diabetes in the NOD mouse. Endocrinology 137, 5567-5575. (Pubitemid 26423125)
33. Nicoletti, F., Di Marco, R., Zaccone, P., Magro, G., Di Mauro, M., Grasso, S., Meroni, P.L., 1999. Endogenous interleukin-12 only plays a key pathogenetic role in non-obese diabetic mouse diabetes during the very early stages of the disease. Immunology 97, 367-370. (Pubitemid 29314630)
34. Offner, H., Firestein, G.S., Boyle, D.L., Pieters, R., Frincke, J.M., Garsd, A., White, S.K., Reading, C.L., Auci, D.L., 2009. An orally bioavailable synthetic analog of an active dehydroepiandrosterone metabolite reduces established disease in rodent models of rheumatoid arthritis. J. Pharmacol. Exp. Ther. 329, 1100-1109.
35. Palmer, J.P., Fleming, G.A., Greenbaum, C.J., Herold, K.C., Jansa, L.D., Kolb, H., Lachin, J.M., Polonsky, K.S., Pozzilli, P., Skyler, J.S., Steffes, M.W., 2004. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes 53, 250-264. (Pubitemid 38044724)
36. Roep, B.O., 2007. Are insights gained from NOD mice sufficient to guide clinical translation? Another inconvenient truth. Ann. NY Acad. Sci. 1103, 1-10.
37. Shoda, L.K., Young, D.L., Ramanujan, S., Whiting, C.C., Atkinson, M.A., Bluestone, J.A., Eisenbarth, G.S., Mathis, D., Rossini, A.A., Campbell, S.E., Kahn, R., Kreuwel, H.T., 2005. A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity 23, 115-126. (Pubitemid 41169282)
38. Svec, F., Porter, J.R., 1998. The actions of exogenous dehydroepiandrosterone in experimental animals and humans. Proc. Soc. Exp. Biol. Med. 218, 174-191.
39. Tang, Q., Bluestone, J.A., 2006. Regulatory T-cell physiology and application to treat autoimmunity. Immunol. Rev. 212, 217-237.
40. Trembleau, S., Penna, G., Gregori, S., Gately, M.K., Adorini, L., 1997. Deviation of pancreas-infiltrating cells to Th2 by interleukin-12 antagonist administration inhibits autoimmune diabetes. Eur. J. Immunol. 27, 2330-2339.
41. Vandenbark, A.A., Offner, H., 2008. Critical evaluation of regulatory T cells in autoimmunity: are the most potent regulatory specificities being ignored? Immunology 125, 1-13.
42. Wang, T., Villegas, S., Huang, Y., White, S.K., Ahlem, C., Lu, M., Olefsky, J.M., Reading, C., Frincke, J.M., Alleva, D., Flores-Riveros, J., 2009. Amelioration of glucose intolerance by the synthetic androstene HE3286: link to inflammatory pathways. J. Pharmacol. Exp. Ther. 333, 70-80.
43. Yang, Z., Chen, M., Ellett, J.D., Fialkow, L.B., Carter, J.D., McDuffie, M., Nadler, J.L., 2004. Autoimmune diabetes is blocked in Stat4-deficient mice. J. Autoimmun. 22, 191-200. (Pubitemid 38369180)
44. Zaccone, P., Phillips, J., Conget, I., Cooke, A., Nicoletti, F., 2005. IL-18 binding protein fusion construct delays the development of diabetes in adoptive transfer and cyclophosphamide-induced diabetes in NOD mouse. Clin. Immunol. 115, 74-79.