In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline compound VGX-1027: Modulation of cytokine synthesis and prevention of both organ-specific and systemic autoimmune diseases in murine models

Clinical Immunology

Volumn 123, Issue 3, 2007, Pages 311-323

  Stojanovic, Ivana ^a   Cuzzocrea, Salvatore ^b,c   Mangano, Katia ^d   Mazzon, Emanuela ^b,c   Miljkovic, Djordje ^a   Wang, Mingjun ^e   Donia, Marco ^d   Al Abed, Yousef ^f   Kim, Joseph ^g   Nicoletti, Ferdinando ^d   Stosic Grujicic, Stanislava ^a   Claesson, Mogens ^e  

^a UNIVERSITY OF BELGRADE   (Serbia)

^b UNIVERSITY OF MESSINA   (Italy)

^c IRCCS CENTRO NEUROLESI BONINO PULEJO   (Italy)

^d UNIVERSITY OF CATANIA   (Italy)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

^f LONG ISLAND JEWISH MEDICAL CENTER   (United States)

^g VGX Pharmaceuticals Inc   (United States)

Author keywords

Carrageenan induced pleurisy; LPS induced lethality; TNF ; Type II collagen induced arthritis; VGX 1027

Indexed keywords

3 PHENYL 4,5 DIHYDRO 5 ISOXAZOLE ACETIC ACID; CARRAGEENAN; CD28 ANTIGEN; CD3 ANTIGEN; CONCANAVALIN A; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 4; ISOXAZOLINE DERIVATIVE; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE P38; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VGX 1027;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTHRITIS; ARTICLE; AUTOIMMUNE DISEASE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG ACTIVITY; DRUG MECHANISM; ENZYME ACTIVATION; EX VIVO STUDY; FEMALE; IMMUNOPHARMACOLOGY; IN VITRO STUDY; IN VIVO STUDY; MACROPHAGE; MALE; MOUSE; NONHUMAN; PLEURISY; PRIORITY JOURNAL; T LYMPHOCYTE;

ACETIC ACIDS; ACETYLMURAMYL-ALANYL-ISOGLUTAMINE; ANIMALS; ARTHRITIS, EXPERIMENTAL; CD4-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; CELL SURVIVAL; CYTOKINES; FEMALE; I-KAPPA B PROTEINS; IMMUNOLOGIC FACTORS; LEUKOCYTES, MONONUCLEAR; LIPOPOLYSACCHARIDES; MACROPHAGES, PERITONEAL; MALE; MICE; MICE, INBRED C57BL; MICE, INBRED CBA; MICE, INBRED DBA; MITOGEN-ACTIVATED PROTEIN KINASES; OXAZOLES; PHOSPHORYLATION; PLEURISY; SHOCK, SEPTIC; SPLEEN; SURVIVAL RATE;

EID: 34249686065     PISSN: 15216616     EISSN: 15217035     Source Type: Journal    
DOI: 10.1016/j.clim.2007.03.004     Document Type: Article

References (47)

1. + regulatory T cells: mechanisms of induction and effector function. Autoimmun. Rev. 4 (2005) 491-496
2. Elenkov I.J., Iezzoni D.G., Daly A., and Harris A.G. Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 12 (2005) 255-269
3. Mouzaki A., Deraos S., and Chatzantoni K. Advances in the treatment of autoimmune diseases; cellular activity, type-1/type-2 cytokine secretion patterns and their modulation by therapeutic peptides. Curr. Med. Chem. 12 (2005) 1537-1550
4. Romagnani S. The Th1/Th2 paradigm. Immunol. Today 18 (1997) 263-266
5. Dumont F.J. Fontolizumab protein design labs. Curr. Opin. Investig. Drugs 6 (2005) 537-544
6. Nishimoto N. Cytokine signal regulation and autoimmune disorders. Autoimmunity 38 (2005) 359-367
7. Miossec P. An update on the cytokine network in rheumatoid arthritis. Curr. Opin. Rheumatol. 16 (2004) 218-222
8. Rabinovitch A., and Suarez-Pinzon W.L. Role of cytokines in the pathogenesis of autoimmune diabetes mellitus. Rev. Endocr. Metab. Disord. 4 (2003) 291-299
9. Alexander H.R., Doherty G.M., Buresh C.M., Venzon D.J., and Norton J.A. A recombinant human receptor antagonist to interleukin 1 improves survival after lethal endotoxemia in mice. J. Exp. Med. 173 (1991) 1029-1032
10. Mohler K.M., Torrance D.S., Smith C.A., Goodwi R.G., Stremler K.E., Fung V.P., Madani H., and Widmer M.B. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J. Immunol. 151 (1993) 1548-1561
11. Buras J.A., Holzmann B., and Sitkovsky M. Animal models of sepsis: setting the stage. Nat. Rev., Drug Discov. 4 (2005) 854-865
12. Arend W.P. The mode of action of cytokine inhibitors. J. Rheumatol. suppl. 65 (2002) 16-21
13. Nash P.T., and Florin T.H. Tumour necrosis factor inhibitors. Med. J. Aust. 18 (2005) 205-208
14. Dinarello C.A. Anti-cytokine therapeutics and infections. Vaccine 21 (2003) S24-S34
15. Wagner G., and Laufer S. Small molecular anti-cytokine agents. Med. Res. Rev. 26 (2006) 1-62
16. Stosic-Grujicic S., Cvetkovic I., Mangano K., Fresta M., Maksimovic-Ivanic D., Harhaji L., Popadic D., Momcilovic M., Miljkovic D., Kim J., Al Abed Y., and Nicoletti F. A potent immunomodulatory compound, (S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid, prevents spontaneous and accelerated forms of autoimmune diabetes in NOD mice and inhibits the immunoinflammatory diabetes induced by multiple low doses of streptozotocin in CBA/H mice. J. Pharmacol. Exp. Ther. 312 (2007) 1-12
17. Cvetkovic I., Al-Abed Y., Miljkovic D., Maksimovic-Ivanic D., Roth J., Bacher M., Lan H.Y., Nicoletti F., and Stosic-Grujicic S. Critical role of macrophage migration inhibitory factor activity in experimental autoimmune diabetes. Endocrinology 146 (2005) 2942-2951
18. Stosic-Grujicic S., Maksimovic D., Badovinac V., Samardzic T., Trajkovic V., and Lukic M. Mostarica Stojkovic M. Antidiabetogenic effect of pentoxifylline is associated with systemic and target tissue modulation of cytokines and nitric oxide production. J. Autoimmun. 16 (2001) 47-58
19. Versteeg H.H., Nijhuis E., van den Brink G.R., Evertzen M., Pynaert G.N., Deventer S.J., Coffer P.J., and Peppelenbosch M.P. A new phosphospecific cell-based ELISA for p42/p44 mitogen-activated protein kinase (MAPK), p38 MAPK, protein kinase B and cAMP-response-element-binding protein. Biochem. J. 350 (2000) 717-722
20. Di Paola R., Di Marco R., Mazzon E., Genovese T., Bendtzen K., Macri B., Nicoletti F., and Cuzzocrea S. Prevention of carrageenan-induced pleurisy in mice by anti-CD30 ligand monoclonal antibody. Clin. Immunol. 113 (2004) 64-73
21. Cuzzocrea S., Mazzon E., Dugo L., Serraino I., Britti D., De Maio M., and Caputi A.P. Absence of endogenous interleukin-10 enhances the evolution of murine type-II collagen-induced arthritis. Eur. Cytokine Netw. 12 (2001) 568-580
22. Cuzzocrea S., Mazzon E., di Paola R., Genovese T., Patel N.S., Britti D., de Majo M., Caputi A.P., and Thiemermann C. Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse. Arthritis Rheum. 52 (2005) 940-950
23. Nakae S., Nambu A., Sudo K., and Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J. Immunol. 171 (2003) 6173-6177
24. Miyake K. Roles for accessory molecules in microbial recognition by Toll-like receptors. J. Endotoxin Res. 12 (2006) 195-204
25. Muzio M., Bosisio D., Polentarutti N., D'amico G., Stoppacciaro A., Mancinelli R., van't Veer C., Penton-Rol G., Ruco L.P., Allavena P., and Mantovani A. Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J. Immunol. 164 (2000) 5998-6004
26. Bagchi A., Herrup E.A., Warren H.S., Trigilio J., Shin H.S., Valentine C., and Hellman J. MyD88-dependent and MyD88-independent pathways in synergy, priming, and tolerance between TLR agonists. J. Immunol. 178 (2007) 1164-1171
27. Werry T.D., Christopoulos A., and Sexton P.M. Mechanisms of ERK1/2 regulation by seven-transmembrane-domain receptors. Curr. Pharm. Des. 12 (2006) 1683-1702
28. Peifer C., Wagner G., and Laufer S. New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38 MAP kinase. Curr. Top. Med. Chem. 6 (2006) 113-149
29. O'Neill L.A. Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. Curr. Opin. Pharmacol. 3 (2003) 396-403
30. Moore K.W., de Wal Malefyt R., Coffman R.L., and O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19 (2001) 683-765
31. Wanidworanun C., and Strober W. Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis. J. Immunol. 151 (1993) 6853-6861
32. Platzer C., Meisel C., Vogt K., Platzer M., and Volk H.D. Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int. Immunol. 7 (1995) 517-523
33. Foey A.D., Crawford A., and Hall N.D. Modulation of cytokine production by human mononuclear cells following impairment of Na, K-ATPase activity. Biochim. Biophys. Acta 1355 (1997) 43-49
34. Groux H., and Cottrez F. The complex role of interleukin-10 in autoimmunity. J. Autoimmun. 20 (2003) 281-285
35. Kaneko T., Itoh M., Nakamura Y., Iimura A., Hyhi S., Takahashi K., Stivala F., Bendtzen K., and Nicoletti F. Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis. Cytokine 22 (2003) 50-53
36. Llorente L., Zou W., Levy Y., Richaud-Patin Y., Wijdenes J., Alcocer-Varela J., Morel-Fourrier B., Brouet J.C., Alarcon-Segovia D., Galanaud P., and Emilie D. Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J. Exp. Med. 181 (1995) 839-844
37. Pennline K.J., Roque-Gaffney E., and Monahan M. Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse. Clin. Immunol. Immunopathol. 71 (1994) 169-175
38. Balasa B., Van Gunst K., Jung N., Katz J.D., and Sarvetnick N. IL-10 deficiency does not inhibit insulitis and accelerates cyclophosphamide-induced diabetes in the nonobese diabetic mouse. Cell. Immunol. 202 (2000) 97-102
39. Goodman R.B., Pugin J., Lee J.S., and Matthay M.A. Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev. 14 (2003) 523-535
40. Brand D.D., Kang A.H., and Rosloniec E.F. Immunopathogenesis of collagen arthritis. Springer Semin. Immunopathol. 25 (2003) 3-18
41. Joosten L.A., Helsen M.M., Saxne T., van De Loo F.A., Heinegard D., and van Den Berg W.B. IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation. J. Immunol. 163 (1999) 5049-5055
42. Gerard C., Bruyns C., Marchant A., Abramowicz D., Vandenabeele P., Delvaux A., Fiers W., Goldman M., and Velu T. Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J. Exp. Med. 177 (1993) 547-550
43. Howard M., Muchamuel T., Andrade S., and Menon S. Interleukin 10 protects mice from lethal endotoxemia. J. Exp. Med. 177 (1993) 1205-1208
44. Cuzzocrea S., Mazzon E., Dugo L., Serraino I., Di Paola R., Genovese T., De Sarro A., and Caputi A.P. Absence of endogenous interleukin-10 enhances the evolution of acute lung injury. Eur. Cytokine Netw. 13 (2002) 285-297
45. Johansson A.C., Hansson A.S., Nandakumar K.S., Backlund J., and Holmdahl R. IL-10 deficient B10.Q mice develop more severe collagen-induced arthritis, but are protected from arthritis induced with anti-type II collagen antibodies. J. Immunol. 167 (2001) 3505-3512
46. Rogy M.A., Auffenberg T., Espat N.J., Philip R., Remick D., Wollenberg G.K., Copeland E.M., and Moldawer L.L. Human tumor necrosis factor receptor (p55) and interleukin 10 gene transfer in the mouse reduces mortality to lethal endotoxemia and also attenuates local inflammatory responses. J. Exp. Med. 181 (1995) 2289-2293
47. Kasama T., Strieter R.M., Lukacs N.W., Lincoln P.M., Burdick M.D., and Kunkel S.L. Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis. J. Clin. Invest. 95 (1995) 2868-2876