TY  - JOUR
AU  - Miljković, Đorđe
AU  - Blazevski, Jana
AU  - Petković, Filip
AU  - Djedović, Neda
AU  - Momcilović, Miljana
AU  - Stanisavljević, Suzana
AU  - Jevtic, Bojan
AU  - Mostarica-Stojković, Marija
AU  - Spasojević, Ivan
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/891
AB  - Dimethyl fumarate (DMF), a new drug for multiple sclerosis (MS) treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. In this article, we examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes. EP efficiently suppressed the release of MS signature cytokines, IFN-gamma and IL-17, from human PBMCs. Furthermore, the production of these cytokines was notably decreased in encephalitogenic T cells after in vivo application of EP to rats. Production of two other proinflammatory cytokines, IL-6 and TNF, and NO was suppressed by EP in macrophages and microglia. Reactive oxygen species production in macrophages, microglia activation, and the development of Ag-presenting phenotype in microglia and macrophages were constrained by EP. The release of IL-6 was reduced in astrocytes. Finally, EP inhibited the activation of transcription factor NF-kappa B in microglia and astrocytes. Most of these effects were also found for DMF, implying that EP and DMF share common targets and mechanisms of action. Importantly, EP had in vivo impact on experimental autoimmune encephalomyelitis, an animal model of MS. Treatment with EP resulted in delay and shortening of the first relapse, and lower clinical scores, whereas the second attack was annihilated. Further studies on the possibility to use EP as an MS therapeutic are warranted.
PB  - Amer Assoc Immunologists, Bethesda
T2  - Journal of Immunology
T1  - A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate
EP  - 2503
IS  - 6
SP  - 2493
VL  - 194
DO  - 10.4049/jimmunol.1402302
ER  - 

@article{
author = "Miljković, Đorđe and Blazevski, Jana and Petković, Filip and Djedović, Neda and Momcilović, Miljana and Stanisavljević, Suzana and Jevtic, Bojan and Mostarica-Stojković, Marija and Spasojević, Ivan",
year = "2015",
abstract = "Dimethyl fumarate (DMF), a new drug for multiple sclerosis (MS) treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. In this article, we examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes. EP efficiently suppressed the release of MS signature cytokines, IFN-gamma and IL-17, from human PBMCs. Furthermore, the production of these cytokines was notably decreased in encephalitogenic T cells after in vivo application of EP to rats. Production of two other proinflammatory cytokines, IL-6 and TNF, and NO was suppressed by EP in macrophages and microglia. Reactive oxygen species production in macrophages, microglia activation, and the development of Ag-presenting phenotype in microglia and macrophages were constrained by EP. The release of IL-6 was reduced in astrocytes. Finally, EP inhibited the activation of transcription factor NF-kappa B in microglia and astrocytes. Most of these effects were also found for DMF, implying that EP and DMF share common targets and mechanisms of action. Importantly, EP had in vivo impact on experimental autoimmune encephalomyelitis, an animal model of MS. Treatment with EP resulted in delay and shortening of the first relapse, and lower clinical scores, whereas the second attack was annihilated. Further studies on the possibility to use EP as an MS therapeutic are warranted.",
publisher = "Amer Assoc Immunologists, Bethesda",
journal = "Journal of Immunology",
title = "A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate",
pages = "2503-2493",
number = "6",
volume = "194",
doi = "10.4049/jimmunol.1402302"
}

Miljković, Đ., Blazevski, J., Petković, F., Djedović, N., Momcilović, M., Stanisavljević, S., Jevtic, B., Mostarica-Stojković, M.,& Spasojević, I.. (2015). A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate. in Journal of Immunology
Amer Assoc Immunologists, Bethesda., 194(6), 2493-2503.
https://doi.org/10.4049/jimmunol.1402302

Miljković Đ, Blazevski J, Petković F, Djedović N, Momcilović M, Stanisavljević S, Jevtic B, Mostarica-Stojković M, Spasojević I. A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate. in Journal of Immunology. 2015;194(6):2493-2503.
doi:10.4049/jimmunol.1402302 .

Miljković, Đorđe, Blazevski, Jana, Petković, Filip, Djedović, Neda, Momcilović, Miljana, Stanisavljević, Suzana, Jevtic, Bojan, Mostarica-Stojković, Marija, Spasojević, Ivan, "A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate" in Journal of Immunology, 194, no. 6 (2015):2493-2503,
https://doi.org/10.4049/jimmunol.1402302 . .