The mannich base NC1153 promotes long-term allograft survival and spares the recipient from multiple toxicities

Journal of Immunology

Volumn 175, Issue 7, 2005, Pages 4236-4246

  Stepkowsld, Stanislaw M ^a   Kao, Judy ^a   Wang, Mou Er ^a   Tejpal, Neelam ^a   Podder, Hemangshu ^a   Furian, Lucrezia ^a   Dimmock, Jonathan ^b   Jha, Amitabh ^b   Das, Umashankar ^b   Kahan, Barry D ^a   Kirken, Robert A ^a,c  

^a UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF SASKATCHEWAN   (Canada)

^c UNIVERSITY OF TEXAS AT EL PASO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOSPORIN A; CYTOCHROME P450 3A4; GROWTH FACTOR RECEPTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 7; JANUS KINASE 2; JANUS KINASE 3; MANNICH BASE; NC 1153; PROLACTIN; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; STAT5A PROTEIN; STAT5B PROTEIN; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CYTOPLASM; DRUG POTENTIATION; ENZYME ACTIVATION; ENZYME SUBSTRATE; GRAFT SURVIVAL; HUMAN; HUMAN CELL; IMMUNE DEFICIENCY; IN VIVO STUDY; KIDNEY ALLOGRAFT; LYMPHOCYTE PROLIFERATION; MAJOR HISTOCOMPATIBILITY COMPLEX; NEPHROTOXICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RECIPIENT; T LYMPHOCYTE ACTIVATION; TRANSPLANTATION TOLERANCE;

EID: 25444525392     PISSN: 00221767     EISSN: None     Source Type: Journal    
DOI: 10.4049/jimmunol.175.7.4236     Document Type: Article

References (74)

1. Kahan, B. D. 2000. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. Lancet 356: 194-202.
2. Gourishankar, S., and P. F. Halloran. 2002. Late deterioration of organ transplants: a problem in injury and homeostasis. Curr. Opin. Immunol. 14: 576-583.
3. Kelly, P., and B. D. Kahan. 2002. Review: metabolism of immunosuppressant drugs. Curr. Drug Meta. 3: 275-287.
4. Kahan, B. D., P. Keown, G. A. Levy, and A. Johnston. 2002. Therapeutic drug monitoring of immunosuppressant drugs in clinical practice. Clin. Ther. 24: 330-350.
5. Bassel-Duby, R., and E. N. Olson. 2003. Role of calcineurin in striated muscle: development, adaptation, and disease. Biochem. Biophys. Res. Commun. 311: 1133-1141.
6. 2+/calcineurin signalling in cells of the immune system. Biochem. Biophys. Res. Commun. 311: 1117-1132.
7. Bennett, W. M., A. DeMattos, M. M. Meyer, T. Andoh, and J. M. Barry. 1996. Chronic cyclosporine nephropathy: the Achilles' heel of immunosuppressive therapy. Kidney Int. 50: 1089-1100.
8. Kahan, B. D. 1989. Cyclosporine. N. Engl. J. Med. 321: 1725-174.
9. Kim, D. H., and D. M. Sabatini. 2004. Raptor and mTOR: subunits of a nutrient-sensitive complex. Curr. Top. Microbiol. Immunol. 279: 259-270.
10. Chen, J. 2004. Novel regulatory mechanisms of mTOR signaling. Curr. Top. Microbiol. Immunol. 279: 245-257.
11. Stepkowski, S. M., L. Tian, K. L. Napoli, R. Ghobrial, M. E. Wang, T. C. Chou, and B. D. Kahan. 1997. Synergistic mechanisms by which sirolimus and cyclosporine inhibit rat heart and kidney allograft rejection. Clin. Exp. Immunol. 108: 63-68.
12. Stepkowski, S. M., K. L. Napoli, M. E. Wang, X. Qu, T-C. Chou, and B. D. Kahan. 1996. Effects of the pharmacokinetic interaction between orally administered sirolimus and cyclosporine on the synergistic prolongation of heart allograft survival in rats. Transplantation 62: 986-994.
13. Napoli, K. L., M. E. Wang, S. M. Stepkowski, and B. D. Kahan. 1998. Relative tissue distributions of cyclosporine and sirolimus after concomitant peroral administration to the rat: evidence for pharmacokinetic interactions. Ther. Drug Monit. 20: 123-133.
14. Podder, H., S. M. Stepkowski, K. L. Napoli, J. Clark, R. R. Verani, T. C. Chou, and B. D. Kahan. 2001. Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine combinations. J. Am. Soc. Nephrol. 12: 1059-1071.
15. + T cells into Th1 and Th2 subsets. J. Immunol. 159: 5802-5809.
16. Kuo, C. T., and J. M. Leiden. 1999. Transcriptional regulation of T lymphocyte development and function. Annu. Rev. Immunol. 17: 149-187.
17. Kane, L. P., J. Lin, and A. Weiss. 2000. Signal transduction by the TCR for antigen. Curr. Opin. Immunol. 12: 242-249.
18. Dallman, M. J., K. J. Wood, K. Hamano, A. R. Bushell, P. J. Morris, M. J. Wood, and H. M. Charlton. 1993. Cytokines and peripheral tolerance to alloantigen. Immunol. Rev. 133: 5-18.
19. Appleman, L. J., and V. A. Boussiotis. 2003. T cell anergy and costimulation. Immunol. Rev. 192: 161-180.
20. Leonard, W. J. 1996. STATs and cytokine specificity. Nat. Med. 2: 968-969.
21. Zhou, Y. J., K. S. Magnuson, T. P. Cheng, M. Gadina, D. M. Frucht, J. Galon, F. Candotti, R. L. Geahlen, P. S. Changelian, and J. J. O'Shea. 2000. Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation. Mol. Cell Biol. 20: 4371-4380.
22. Nelson, B. H., and D. M. Willerford. 1998. Biology of the interleukin-2 receptor. Adv. Immunol. 70: 1-81.
23. Bromberg, J., and J. E. Darnell Jr. 2000. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19: 2468-2473.
24. Lin, J. X., and W. J. Leonard. 2000. The role of Stat5a and Stat5b in signaling by IL-2 family cytokines. Oncogene 19: 2566-2576.
25. Behbod, F., R. A. Erwin-Cohen, M. E. Wang, B. W. Trawick, X. Qu, R. Verani, B. D. Kahan, S. M. Stepkowski, and R. A. Kirken. 2001. Concomitant inhibition of JAK3 and calcineurin-dependent signaling pathways synergistically prolongs the survival of rat heart allografts. J. Immunol. 166: 3724-3732.
26. Stepkowski, S. M., R. A. Erwin-Cohen, F. Behbod, M. E. Wang, X. Qu, N. Tejpal, Z. S. Nagy, B. D. Kahan, and R. A. Kirken. 2002. Selective inhibitor of Janus tyrosine kinase 3, PNU156804, prolongs allograft survival and acts synergistically with cyclosporine but additively with rapamycin. Blood 99: 680-689.
27. Changelian, P. S., M. E. Flanagan, D. J. Ball, C. R. Kent, K. S. Magnuson, W. H. Martin, B. J. Rizzuti, P. S. Sawyer, B. D. Perry, W. H. Brissette, et al. 2003. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 302: 875-878.
28. Thomis, D. C., and L. J. Berg. 1997. Peripheral expression of Jak3 is required to maintain T lymphocyte function. J. Exp. Med. 185: 197-206.
29. Thomis, D. C., W. Lee, and L. J. Berg. 1997. T cells from Jak3-deficient mice have intact TCR signaling, but increased apoptosis. J. Immunol. 159:4708-4719.
30. Russell, S. M., J. A. Johnston, M. Noguchi, M. Kawamura, C. M. Bacon, M. Friedmann, M. Berg, D. W. McVicar, B. A. Witthuhn, O. Silvennoinen, et al. 1994. Interaction of IL-2R β and γ c chains with Jak1 and Jak3: implications for XSCID and XCID. Science 266: 1042-1045.
31. Uckun, F. M., B. A. Roers, B. Waurzyniak, X. P. Liu, and M. Cetkovic-Cvrlje. 2002. Janus kinase 3 inhibitor WHI-P131/JANEX-1 prevents graft-versus-host disease but spares the graft-versus-leukemia function of the bone marrow allografts in a murine bone marrow transplantation model. Blood 99: 4192-4199.
32. Kuhn, B., W. Jacobsen, U. Christians, L. Z. Benet, and P. A. Kollman. 2001. Metabolism of sirolimus and its derivative everolimus by cytochrome P450 3A4: insights from docking, molecular dynamics, and quantum chemical calculations. J. Med. Chem. 44: 2027-2034.
33. Sattler, M., F. P. Guengerich, C. H. Yun, U. Christians, and K. F. Sewing. 1992. Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab. Dispos. 20: 753-761.
34. Kirken, R. A., R. A. Erwin, D. Taub, W. J. Murphy, F. Behbod, L. Wang, F. Pericle, and W. L. Farrar. 1999. Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells. J. Leukocyte Biol. 65: 891-899.
35. Dimmock, J. R., M. Chamankhah, A. Seniuk, T. M. Allen, G. Y. Kao, and S. Halleran. 1995. Synthesis and cytotoxic evaluation of some Mannich bases of alicyclic ketones. Pharmazie 50: 668-671.
36. Pericle, F., R. A. Kirken, V. Bronte, G. Sconocchia, L. DaSilva, and D. M. Segal. 1997. Immunocompromised tumor bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes. J. Immunol. 159: 2580-2585.
37. 730 of Stat5b in prolactin-sensitive cells. J. Biol. Chem. 273: 30218-30218.
38. Kirken, R. A., H. Rui, M. G. Malabarba, O. M. Z. Howard, M. Kawamura, J. J. O'Shea, and W. L. Farrar WL. 1995. Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and STATS recruitment by a COOH-terminal region of the IL-2 receptor β-chain. Cytokine 7: 689-700.
39. Tian, L., S. M. Stepkowski, X. Qu, M. E. Wang, M. Wang, J. Yu, and B. D. Kahan. 1997. Cytokine mRNA expression in tolerant heart allografts after immunosuppression with cyclosporine, sirolimus or brequinar. Transpl. Immunol. 5: 189-198.
40. Kirken, R. A., H. Rui, G. A. Evans, and W. L. Farrar. 1993. Characterization of an interleukin-2 (IL-2)-induced tyrosine phosphorylated 116-kDa protein associated with the IL-2 receptor β-subunit. J. Biol. Chem. 268: 22765-22770.
41. Rodrigues, A. D. 1999. Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochem. Pharmacol. 57: 465-480.
42. Chou, T.-C. 1991. The median effect principle and the combination index for quantitation of synergism and antagonism. In Synergism and Antagonism in Chemotherapy. T.-C. Chou and D. Rideout, eds. Academic Press, San Diego, pp. 61-102.
43. Chou, J., and T.-C. Chou. 1987. Dose-effect analysis with microcomputers: quantitation of ED50, LD50, synergism, antagonism, low-dose risk, receptor-ligand binding and enzyme kinetics. In Biosoft. Cambridge.
44. Schrader, B., and G. Steinhoff. 1993. Models of inflammatory cascade reactions by adhesion molecules. In Cell Adhesion Molecules in Human Organ Transplants. G. Steinhoff, ed. R. G. Lands, Austin, pp. 71-86.
45. Boyd, M. 1995. The NCI in vitro anticancer drug discovery screen. In Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval. B. Teicher, ed. Humana Press, Totowa, pp. 23-42.
46. Malabarba, M. G., H. Rui, H. H. Deutsch, J. Chung, F. S. Kalthoff, W. L. Farrar, and R. A. Kirken. 1996. Interleukin-13 is a potent activator of JAK3 and STAT6 in cells expressing interleukin-2 receptor-γ and interleukin-4 receptor-α. Biochem. J. 319: 865-872.
47. Malabarba, M. G., R. A. Kirken, H. Rui, K. Koettnitz, M. Kawamura, J. J. O'Shea, F. S. Kaltoff, and W. L. Farrar. 1995. Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor α. J. Biol. Chem. 270: 9630-9637.
48. Zhou, Y. J., E. P. Hanson, Y. Q. Chen, K. Magnuson, M. Chen, P. G. Swann, R. L. Wange, P. S. Changelian, and J. J. O'Shea. 1997. Distinct tyrosine phosphorylation sites in JAK3 kinase domain positively and negatively regulate its enzymatic activity. Proc. Natl. Acad. Sci. USA 94: 13850-13850.
49. Moriggl, R., D. J. Topham, S. Teglund, V. Sexl, C. McKay, D. Wang, A. Hoffmeyer, J. van Deursen, M. Y. Sangster, K. D. Bunting, et al. 1999. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10: 249-259.
50. Higuchi, M., H. Asao, N. Tanaka, K. Oda, T. Takeshita, M. Nakamura, J. Van Snick, and K. Sugamura. 1996. Dispensability of Jakl tyrosine kinase for interleukin-2-induced cell growth signaling in a human T cell line. Eur. J. Immunol. 26: 1322-1327.
51. Evans, G. A., M. A. Goldsmith, J. A. Johnston, W. D. Xu, S. R. Weiler, R. Erwin, O. M. Z. Howard, R. T. Abraham, J. J. O'Shea, W. C. Green, and W. L. Farrar. 1995. Analysis of interleukin 2 dependent signal transduction through the SHC/GRB2 adapter pathway-interleukin-2-dependent mitogenesis does not require SHC phosphorylation or receptor association. J. Biol. Chem 270: 28858-28863.
52. Howard, O. M. Z., R. A. Kirken, G. G. Garcia, R. H. Hackett, and W. L. Farrar. 1995. Structural domains of IL-2 receptor β critical for signal transduction: kinase association and nuclear complex formation. Biochem. J. 306: 217-224.
53. Salcini, A. E., J. McGlade, G. Pelicci, I. Nicoletti, T. Pawson, and P. G. Pelicci. 1994. Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of She proteins. Oncogene 9: 2827-2836.
54. Gotoh, N., A. Tojo, and M. Shibuya. 1996. A novel pathway from phosphorylation of tyrosine residues 239/240 of She, contributing to suppress apoptosis by IL-3. EMBO J. 15: 6197-6204.
55. Darnell, J. E. Jr. 1997. STATs and gene regulation. Science 277: 1630-1635.
56. Cheung, J. Y., and B. A. Miller. 2001. Molecular mechanisms of erythropoietin signaling. Nephron 87: 215-222.
57. Lacombe, C., and P. Mayeux. 1999. The molecular biology of erythropoietin. Nephrol. Dial. Transplant. 14: 22-28.
58. Wendling, F., and W. Vainchenker. 1998. Thrombopoietin and its receptor. Eur. Cytokine Netw. 9: 221-231.
59. Kirken, R. A., H. Rui, M. G. Malabarba, and W. L. Farrar. 1994. Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel leukocyte-specific Janus kinase. J. Biol. Chem. 269: 19136-19141.
60. Hesselink, D. A., R. H. van Schaik, I. P. van der Heiden, M. van der Werf, P. J. Gregoor, J. Lindemans, W. Weimar, and T. van Gelder. 2003. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin. Pharmacol. Ther. 74: 245-254.
61. English, J., A. Evan, D. C. Houghton, and W. M Bennett. 1987. Cyclosporine-induced acute renal dysfunction in the rat: evidence of arteriolar vasoconstriction with preservation of tubular function. Transplantation 44: 135-141.
62. Mason, J. 1990. The pathophysiology of Sandimmune (cyclosporine) in man and animals. Pediatr. Nephrol. 4: 554-574.
63. Baud, L., and R. Ardaillou. 1993. Involvement of reactive oxygen species in kidney damage. Br. Med. Bull. 49: 621-629.
64. Serino, F., J. Grevel, K. L. Napoli, B. D. Kahan, and H. W. Strobel. 1994. Oxygen radical formation by the cytochrome P450 system as a cellular mechanism for cyclosporine toxicity. Transplant. Proc. 26: 2916-2917.
65. Shin, G. T., A. Khanna, R. Ding, V. K. Sharma, M. Lagman, B. Li, and M. Suthanthiran. 1998. In vivo expression of transforming growth factor-β1 in humans: stimulation by cyclosporine. Transplantation 65: 313-318.
66. Avdonin, P. V., F. Cottet-Maire, G. V. Afanasjeva, S. A. Loktionova, P. Lhote, and U. T. Ruegg. 1999. Cyclosporine A up-regulates angiotensin II receptors and calcium responses in human vascular smooth muscle cells. Kidney Int. 55: 2407-2414.
67. Vaziri, N. D., Z. Ni, Y. P. Zhang, E. P. Ruzics, P. Maleki, and Y. Ding. 1998. Depressed renal and vascular nitric oxide synthase expression in cyclosporine-induced hypertension. Kidney Int. 54: 482-491.
68. Healy, E., M. Dempsey, C. Lally, and M. P. Ryan. 1998. Apoptosis and necrosis: mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line. Kidney Int. 54: 1955-1966.
69. Ortiz, A., C. Lorz, M. Catalan, A. Ortiz, S. Coca, and J. Egido. 1998. Cyclosporine A induces apoptosis in murine tubular epithelial cells: role of caspases. Kidney Int. 68(Suppl.): S25-S29.
70. Groth, C. G., L. Backman, J. M. Morales, R. Calne, H. Kreis, P. Lang, J. L. Tourine, K. Claesson, J. M. Campistol, D. Durand, et al. 1999. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation 67: 1036-1042.
71. Murgia, M. G., S. Jordan, and B. D. Kahan. 1996. The side effect profile of sirolimus: a phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients. Kidney Int. 49: 209-216.
72. Bunting, K. D., M. Y. Sangster, J. N. Ihle, and B. P. Sorrentino. 1998. Restoration of lymphocyte function in Janus kinase 3-deficient mice by retroviral-mediated gene transfer. Nat. Med. 4: 58-64.
73. Behbod, F., Z. S. Nagy, S. M. Stepkowski, J. Karras, C. R. Johnson, W. D. Jarvis, and R. A. Kirken. 2003. Specific inhibition of Stat5a/b promotes apoptosis of IL-2-responsive primary and tumor-derived lymphoid cells. J. Immunol. 171: 3919-3927.
74. + regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22: 531-562.