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 . .