TY  - JOUR
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
AU  - Mangano,  Katia
AU  - Fresta, Massimo
AU  - Maksimović-Ivanić, Danijela
AU  - Harhaji-Trajković, Ljubica
AU  - Popadić, Dušan
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Kim, Joseph
AU  - Al-Abed, Yousef
AU  - Nicoletti,  Ferdinando
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3824
AB  - (S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) is an isoxazole compound that exhibits various immunomodulatory properties. The capacity of VGX-1027 to prevent interleukin (IL)-1beta plus interferon-gamma-induced pancreatic islet death in vitro prompted us to evaluate its effects on the development of autoimmune diabetes in preclinical models of human type 1 diabetes mellitus (T1D). Administration of VGX-1027 to NOD mice with spontaneous or accelerated forms of diabetes induced either by injection of cyclophosphamide or by transfer of spleen cells from acutely diabetic syngeneic donors markedly reduced the cumulative incidence of diabetes and insulitis. In addition, VGX-1027 given either i.p. or p.o. to CBA/H mice made diabetic with multiple low doses of streptozotocin successfully counteracted the development of destructive insulitis and hyperglycemia. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. These results indicate that VGX-1027 probably exerts its antidiabetogenic effects by limiting cytokine-mediated immunoinflammatory events, leading to inflammation and destruction of pancreatic islets. VGX-1027 seems worthy of being considered as a candidate drug in the development of new therapeutic strategies for the prevention and early treatment of T1D.
PB  - Rockville: American Society for Pharmacology and Experimental Therapeutics (ASPET)
T2  - Journal of Pharmacology and Experimental Therapeutics
T1  - A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole 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
IS  - 3
VL  - 320
DO  - 10.1124/jpet.106.109272
SP  - 1038
EP  - 1049
ER  - 

@article{
author = "Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Mangano,  Katia and Fresta, Massimo and Maksimović-Ivanić, Danijela and Harhaji-Trajković, Ljubica and Popadić, Dušan and Momčilović, Miljana and Miljković, Đorđe and Kim, Joseph and Al-Abed, Yousef and Nicoletti,  Ferdinando",
year = "2007",
abstract = "(S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) is an isoxazole compound that exhibits various immunomodulatory properties. The capacity of VGX-1027 to prevent interleukin (IL)-1beta plus interferon-gamma-induced pancreatic islet death in vitro prompted us to evaluate its effects on the development of autoimmune diabetes in preclinical models of human type 1 diabetes mellitus (T1D). Administration of VGX-1027 to NOD mice with spontaneous or accelerated forms of diabetes induced either by injection of cyclophosphamide or by transfer of spleen cells from acutely diabetic syngeneic donors markedly reduced the cumulative incidence of diabetes and insulitis. In addition, VGX-1027 given either i.p. or p.o. to CBA/H mice made diabetic with multiple low doses of streptozotocin successfully counteracted the development of destructive insulitis and hyperglycemia. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. These results indicate that VGX-1027 probably exerts its antidiabetogenic effects by limiting cytokine-mediated immunoinflammatory events, leading to inflammation and destruction of pancreatic islets. VGX-1027 seems worthy of being considered as a candidate drug in the development of new therapeutic strategies for the prevention and early treatment of T1D.",
publisher = "Rockville: American Society for Pharmacology and Experimental Therapeutics (ASPET)",
journal = "Journal of Pharmacology and Experimental Therapeutics",
title = "A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole 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",
number = "3",
volume = "320",
doi = "10.1124/jpet.106.109272",
pages = "1038-1049"
}

Stošić-Grujičić, S., Stojanović, I. D., Mangano,  ., Fresta, M., Maksimović-Ivanić, D., Harhaji-Trajković, L., Popadić, D., Momčilović, M., Miljković, Đ., Kim, J., Al-Abed, Y.,& Nicoletti,  .. (2007). A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole 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. in Journal of Pharmacology and Experimental Therapeutics
Rockville: American Society for Pharmacology and Experimental Therapeutics (ASPET)., 320(3), 1038-1049.
https://doi.org/10.1124/jpet.106.109272

Stošić-Grujičić S, Stojanović ID, Mangano  , Fresta M, Maksimović-Ivanić D, Harhaji-Trajković L, Popadić D, Momčilović M, Miljković Đ, Kim J, Al-Abed Y, Nicoletti  . A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole 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. in Journal of Pharmacology and Experimental Therapeutics. 2007;320(3):1038-1049.
doi:10.1124/jpet.106.109272 .

Stošić-Grujičić, Stanislava, Stojanović, Ivana D., Mangano,  Katia, Fresta, Massimo, Maksimović-Ivanić, Danijela, Harhaji-Trajković, Ljubica, Popadić, Dušan, Momčilović, Miljana, Miljković, Đorđe, Kim, Joseph, Al-Abed, Yousef, Nicoletti,  Ferdinando, "A potent immunomodulatory compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole 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" in Journal of Pharmacology and Experimental Therapeutics, 320, no. 3 (2007):1038-1049,
https://doi.org/10.1124/jpet.106.109272 . .

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Cuzzocrea, S
AU  - Mangano, Katia
AU  - Mazzon, E
AU  - Miljković, Đorđe
AU  - Wang, MJ
AU  - Donia, Marco
AU  - Al-Abed, Yousef
AU  - Kim, Joseph
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
AU  - Claesson, MH
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1598
AB  - We have presently studied the in vitro, ex vivo and in vivo immunopharmacological effects of VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid]. This compound reduced the secretion of IL-1 beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappa B and p38 MAP kinase pathways along with up-regulation of ERK pathways. VGX-1027 appeared to spare T cell function as it was unable to modify the proliferation and/or secretion of IL-2, IFN-gamma and IL-4 induced in purified murine CD4(+) T cells from stimulation with either CD3(+)CD28 or ConA. These effects on macrophages may account for the capacity of VGX-1027 to markedly ameliorate the course of both acute and chronic immunoinflammatory diseases in mice such as carrageenan-induced pleurisy, LPS-induced lethality and type II collagen-induced arthritis. Acute and subacute toxicological studies show that the drug is not toxic at the doses that exert biological effects in these preclinical models. These data warrant additional studies for the potential use of VGX-1027 in the clinical setting. (C) 2007 Elsevier Inc. All rights reserved.
T2  - Clinical Immunology
T1  - 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
IS  - 3
VL  - 123
EP  - 323
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1598
ER  - 

@article{
author = "Stojanović, Ivana D. and Cuzzocrea, S and Mangano, Katia and Mazzon, E and Miljković, Đorđe and Wang, MJ and Donia, Marco and Al-Abed, Yousef and Kim, Joseph and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava and Claesson, MH",
year = "2007",
abstract = "We have presently studied the in vitro, ex vivo and in vivo immunopharmacological effects of VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid]. This compound reduced the secretion of IL-1 beta, TNF-alpha and IL-10 from purified murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it also modified the signaling pathways induced in these cells by LPS entailing reduced activation of NF-kappa B and p38 MAP kinase pathways along with up-regulation of ERK pathways. VGX-1027 appeared to spare T cell function as it was unable to modify the proliferation and/or secretion of IL-2, IFN-gamma and IL-4 induced in purified murine CD4(+) T cells from stimulation with either CD3(+)CD28 or ConA. These effects on macrophages may account for the capacity of VGX-1027 to markedly ameliorate the course of both acute and chronic immunoinflammatory diseases in mice such as carrageenan-induced pleurisy, LPS-induced lethality and type II collagen-induced arthritis. Acute and subacute toxicological studies show that the drug is not toxic at the doses that exert biological effects in these preclinical models. These data warrant additional studies for the potential use of VGX-1027 in the clinical setting. (C) 2007 Elsevier Inc. All rights reserved.",
journal = "Clinical Immunology",
title = "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",
number = "3",
volume = "123",
pages = "323",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1598"
}

Stojanović, I. D., Cuzzocrea, S., Mangano, K., Mazzon, E., Miljković, Đ., Wang, M., Donia, M., Al-Abed, Y., Kim, J., Nicoletti, F., Stošić-Grujičić, S.,& Claesson, M.. (2007). 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. in Clinical Immunology, 123(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1598

Stojanović ID, Cuzzocrea S, Mangano K, Mazzon E, Miljković Đ, Wang M, Donia M, Al-Abed Y, Kim J, Nicoletti F, Stošić-Grujičić S, Claesson M. 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. in Clinical Immunology. 2007;123(3):null-323.
https://hdl.handle.net/21.15107/rcub_ibiss_1598 .

Stojanović, Ivana D., Cuzzocrea, S, Mangano, Katia, Mazzon, E, Miljković, Đorđe, Wang, MJ, Donia, Marco, Al-Abed, Yousef, Kim, Joseph, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, Claesson, MH, "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" in Clinical Immunology, 123, no. 3 (2007),
https://hdl.handle.net/21.15107/rcub_ibiss_1598 .