TY  - JOUR
AU  - Gajić, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Šenerović, Lidija
AU  - Morić, Ivana
AU  - Šavikin, Katarina
AU  - Menković, Nebojša
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1638
AB  - Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiation in vitro. When applied orally to healthy mice, CE increased the proportion of CD11c+ dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingested Listeria monocytogenes as evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b+ macrophages and CD8+ cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86+ macrophages (CD11b+) and dendritic cells (CD11c+) was also enhanced in CE-pretreated infected mice. Further, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and the similar results were obtained in peritoneal macrophages in vitro. This effect of CE was associated with increased phosphorylation of IκB and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection with Listeria monocytogenes predominantly through increased activity of myeloid cells in the gut and in the spleen.
PB  - United Kingdom : Royal Society of Chemistry
T2  - Food and Function
T1  - Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice
EP  - 7803
IS  - 9
SP  - 7793
VL  - 11
DO  - 10.1039/D0FO00946F
ER  - 

@article{
author = "Gajić, Dragica and Saksida, Tamara and Koprivica, Ivan and Šenerović, Lidija and Morić, Ivana and Šavikin, Katarina and Menković, Nebojša and Pejnović, Nada and Stojanović, Ivana D.",
year = "2020",
abstract = "Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiation in vitro. When applied orally to healthy mice, CE increased the proportion of CD11c+ dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingested Listeria monocytogenes as evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b+ macrophages and CD8+ cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86+ macrophages (CD11b+) and dendritic cells (CD11c+) was also enhanced in CE-pretreated infected mice. Further, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and the similar results were obtained in peritoneal macrophages in vitro. This effect of CE was associated with increased phosphorylation of IκB and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection with Listeria monocytogenes predominantly through increased activity of myeloid cells in the gut and in the spleen.",
publisher = "United Kingdom : Royal Society of Chemistry",
journal = "Food and Function",
title = "Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice",
pages = "7803-7793",
number = "9",
volume = "11",
doi = "10.1039/D0FO00946F"
}

Gajić, D., Saksida, T., Koprivica, I., Šenerović, L., Morić, I., Šavikin, K., Menković, N., Pejnović, N.,& Stojanović, I. D.. (2020). Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice. in Food and Function
United Kingdom : Royal Society of Chemistry., 11(9), 7793-7803.
https://doi.org/10.1039/D0FO00946F

Gajić D, Saksida T, Koprivica I, Šenerović L, Morić I, Šavikin K, Menković N, Pejnović N, Stojanović ID. Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice. in Food and Function. 2020;11(9):7793-7803.
doi:10.1039/D0FO00946F .

Gajić, Dragica, Saksida, Tamara, Koprivica, Ivan, Šenerović, Lidija, Morić, Ivana, Šavikin, Katarina, Menković, Nebojša, Pejnović, Nada, Stojanović, Ivana D., "Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice" in Food and Function, 11, no. 9 (2020):7793-7803,
https://doi.org/10.1039/D0FO00946F . .

TY  - JOUR
AU  - Gajić, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Šenerović, Lidija
AU  - Morić, Ivana
AU  - Savikin, Katarina
AU  - Menković, Nebojša
AU  - Pejnović, Nada
AU  - Stojanović, Ivana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1366
AB  - Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiationin vitro. When applied orally to healthy mice, CE increased the proportion of CD11c(+)dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingestedListeria monocytogenesas evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b(+)macrophages and CD8(+)cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86(+)macrophages (CD11b(+)) and dendritic cells (CD11c(+)) were also enhanced in CE-pretreated infected mice. Furthermore, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and similar results were obtained in peritoneal macrophagesin vitro. This effect of CE was associated with increased phosphorylation of I kappa B and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection withL. monocytogenespredominantly through increased activity of myeloid cells in the gut and in the spleen.
PB  - Royal Soc Chemistry, Cambridge
T2  - Food & Function
T1  - Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice
EP  - 7803
IS  - 9
SP  - 7793
VL  - 11
DO  - 10.1039/d0fo00946f
ER  - 

@article{
author = "Gajić, Dragica and Saksida, Tamara and Koprivica, Ivan and Šenerović, Lidija and Morić, Ivana and Savikin, Katarina and Menković, Nebojša and Pejnović, Nada and Stojanović, Ivana",
year = "2020",
abstract = "Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiationin vitro. When applied orally to healthy mice, CE increased the proportion of CD11c(+)dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingestedListeria monocytogenesas evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b(+)macrophages and CD8(+)cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86(+)macrophages (CD11b(+)) and dendritic cells (CD11c(+)) were also enhanced in CE-pretreated infected mice. Furthermore, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and similar results were obtained in peritoneal macrophagesin vitro. This effect of CE was associated with increased phosphorylation of I kappa B and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection withL. monocytogenespredominantly through increased activity of myeloid cells in the gut and in the spleen.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Food & Function",
title = "Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice",
pages = "7803-7793",
number = "9",
volume = "11",
doi = "10.1039/d0fo00946f"
}

Gajić, D., Saksida, T., Koprivica, I., Šenerović, L., Morić, I., Savikin, K., Menković, N., Pejnović, N.,& Stojanović, I.. (2020). Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice. in Food & Function
Royal Soc Chemistry, Cambridge., 11(9), 7793-7803.
https://doi.org/10.1039/d0fo00946f

Gajić D, Saksida T, Koprivica I, Šenerović L, Morić I, Savikin K, Menković N, Pejnović N, Stojanović I. Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice. in Food & Function. 2020;11(9):7793-7803.
doi:10.1039/d0fo00946f .

Gajić, Dragica, Saksida, Tamara, Koprivica, Ivan, Šenerović, Lidija, Morić, Ivana, Savikin, Katarina, Menković, Nebojša, Pejnović, Nada, Stojanović, Ivana, "Immunomodulatory activity and protective effects of chokeberry fruit extract onListeria monocytogenesinfection in mice" in Food & Function, 11, no. 9 (2020):7793-7803,
https://doi.org/10.1039/d0fo00946f . .

TY  - JOUR
AU  - Vujicić, Milica
AU  - Saksida, Tamara
AU  - Despotović, Sanja
AU  - Soković Bajić, Svetlana
AU  - Lalić, Ivana
AU  - Koprivica, Ivan
AU  - Gajić, Dragica
AU  - Golić, Nataša
AU  - Tolinački, Maja
AU  - Stojanović, Ivana
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1182
AB  - Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-gamma in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function.
PB  - Nature Publishing Group, London
T2  - Scientific Reports
T1  - The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier
VL  - 8
DO  - 10.1038/s41598-018-24706-3
ER  - 

@article{
author = "Vujicić, Milica and Saksida, Tamara and Despotović, Sanja and Soković Bajić, Svetlana and Lalić, Ivana and Koprivica, Ivan and Gajić, Dragica and Golić, Nataša and Tolinački, Maja and Stojanović, Ivana",
year = "2018",
abstract = "Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-gamma in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function.",
publisher = "Nature Publishing Group, London",
journal = "Scientific Reports",
title = "The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier",
volume = "8",
doi = "10.1038/s41598-018-24706-3"
}

Vujicić, M., Saksida, T., Despotović, S., Soković Bajić, S., Lalić, I., Koprivica, I., Gajić, D., Golić, N., Tolinački, M.,& Stojanović, I.. (2018). The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier. in Scientific Reports
Nature Publishing Group, London., 8.
https://doi.org/10.1038/s41598-018-24706-3

Vujicić M, Saksida T, Despotović S, Soković Bajić S, Lalić I, Koprivica I, Gajić D, Golić N, Tolinački M, Stojanović I. The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier. in Scientific Reports. 2018;8.
doi:10.1038/s41598-018-24706-3 .

Vujicić, Milica, Saksida, Tamara, Despotović, Sanja, Soković Bajić, Svetlana, Lalić, Ivana, Koprivica, Ivan, Gajić, Dragica, Golić, Nataša, Tolinački, Maja, Stojanović, Ivana, "The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier" in Scientific Reports, 8 (2018),
https://doi.org/10.1038/s41598-018-24706-3 . .

TY  - JOUR
AU  - Vujicić, Milica
AU  - Šenerović, Lidija
AU  - Nikolić, Ivana
AU  - Saksida, Tamara
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/717
AB  - Macrophage migration inhibitory factor (MIF) is a molecule with plethora of functions such as regulation of immune response, hormone-like, enzymatic and chaperone-like activity. Further, MIF is a major participant in glucose homeostasis since it is an autocrine stimulator of insulin secretion. MIF absence in male knockout mice (MW-MO) results in development of glucose intolerance, while sensitivity to insulin is fully preserved. Since our results confirm that beta cells from MIF-KO mice express, produce and secrete insulin similarly to beta cells of their wild type (WT) counterparts C57BL/6 mice, we hypothesize that MIF-KO-derived insulin is less active. Indeed, insulin from MIF-KO islets is unable to significantly induce glucose uptake into hepatocytes and to efficiently promote insulin-triggered Akt phosphorylation determined by immunoblot. However, MIF's tautomerase function is not crucial for insulin biosynthesis since MIF inhibitors had no impact on WT insulin activity. Importantly, MIF recognition by anti-MIF anti-body (ELISA) after in vitro co-incubation with purified insulin was significantly lower suggesting that insulin covers MIF immunodominant epitope. In addition, MIF binds insulin within beta cell as confirmed by co-immunoprecipitation. WT and MIF-KO-derived insulin exhibited different cleavage patterns suggesting different protein conformations. Finally, pre-incubation of recombinant MIF with insulin promotes formation of insulin hexamers. These results imply that MIF probably enables proper insulin folding what results in insulin full activity. This newly discovered feature of the cytokine MIF could be potentially important for commercially produced insulin, for increasing its stability and/or bioavailability.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Cytokine
T1  - The critical role of macrophage migration inhibitory factor in insulin activity
EP  - 46
IS  - 1
SP  - 39
VL  - 69
DO  - 10.1016/j.cyto.2014.05.013
ER  - 

@article{
author = "Vujicić, Milica and Šenerović, Lidija and Nikolić, Ivana and Saksida, Tamara and Stošić-Grujičić, Stanislava and Stojanović, Ivana",
year = "2014",
abstract = "Macrophage migration inhibitory factor (MIF) is a molecule with plethora of functions such as regulation of immune response, hormone-like, enzymatic and chaperone-like activity. Further, MIF is a major participant in glucose homeostasis since it is an autocrine stimulator of insulin secretion. MIF absence in male knockout mice (MW-MO) results in development of glucose intolerance, while sensitivity to insulin is fully preserved. Since our results confirm that beta cells from MIF-KO mice express, produce and secrete insulin similarly to beta cells of their wild type (WT) counterparts C57BL/6 mice, we hypothesize that MIF-KO-derived insulin is less active. Indeed, insulin from MIF-KO islets is unable to significantly induce glucose uptake into hepatocytes and to efficiently promote insulin-triggered Akt phosphorylation determined by immunoblot. However, MIF's tautomerase function is not crucial for insulin biosynthesis since MIF inhibitors had no impact on WT insulin activity. Importantly, MIF recognition by anti-MIF anti-body (ELISA) after in vitro co-incubation with purified insulin was significantly lower suggesting that insulin covers MIF immunodominant epitope. In addition, MIF binds insulin within beta cell as confirmed by co-immunoprecipitation. WT and MIF-KO-derived insulin exhibited different cleavage patterns suggesting different protein conformations. Finally, pre-incubation of recombinant MIF with insulin promotes formation of insulin hexamers. These results imply that MIF probably enables proper insulin folding what results in insulin full activity. This newly discovered feature of the cytokine MIF could be potentially important for commercially produced insulin, for increasing its stability and/or bioavailability.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Cytokine",
title = "The critical role of macrophage migration inhibitory factor in insulin activity",
pages = "46-39",
number = "1",
volume = "69",
doi = "10.1016/j.cyto.2014.05.013"
}

Vujicić, M., Šenerović, L., Nikolić, I., Saksida, T., Stošić-Grujičić, S.,& Stojanović, I.. (2014). The critical role of macrophage migration inhibitory factor in insulin activity. in Cytokine
Academic Press Ltd- Elsevier Science Ltd, London., 69(1), 39-46.
https://doi.org/10.1016/j.cyto.2014.05.013

Vujicić M, Šenerović L, Nikolić I, Saksida T, Stošić-Grujičić S, Stojanović I. The critical role of macrophage migration inhibitory factor in insulin activity. in Cytokine. 2014;69(1):39-46.
doi:10.1016/j.cyto.2014.05.013 .

Vujicić, Milica, Šenerović, Lidija, Nikolić, Ivana, Saksida, Tamara, Stošić-Grujičić, Stanislava, Stojanović, Ivana, "The critical role of macrophage migration inhibitory factor in insulin activity" in Cytokine, 69, no. 1 (2014):39-46,
https://doi.org/10.1016/j.cyto.2014.05.013 . .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Miljković, Djordje
AU  - Timotijević, Gordana
AU  - Stojanović, Ivana
AU  - Mijatović, Sanja
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Mammana, Santa
AU  - Farina, Claudio
AU  - Ascione, Ester
AU  - Maiello, Valentina
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/627
AB  - Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1 beta, TNF, INF-gamma, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3(+) T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NF kappa B signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis.
PB  - Elsevier, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis
EP  - 78
IS  - 1-2
SP  - 72
VL  - 262
DO  - 10.1016/j.jneuroim.2013.07.001
ER  - 

@article{
author = "Saksida, Tamara and Miljković, Djordje and Timotijević, Gordana and Stojanović, Ivana and Mijatović, Sanja and Fagone, Paolo and Mangano, Katia and Mammana, Santa and Farina, Claudio and Ascione, Ester and Maiello, Valentina and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2013",
abstract = "Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1 beta, TNF, INF-gamma, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3(+) T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NF kappa B signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis",
pages = "78-72",
number = "1-2",
volume = "262",
doi = "10.1016/j.jneuroim.2013.07.001"
}

Saksida, T., Miljković, D., Timotijević, G., Stojanović, I., Mijatović, S., Fagone, P., Mangano, K., Mammana, S., Farina, C., Ascione, E., Maiello, V., Nicoletti, F.,& Stošić-Grujičić, S.. (2013). Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology
Elsevier, Amsterdam., 262(1-2), 72-78.
https://doi.org/10.1016/j.jneuroim.2013.07.001

Saksida T, Miljković D, Timotijević G, Stojanović I, Mijatović S, Fagone P, Mangano K, Mammana S, Farina C, Ascione E, Maiello V, Nicoletti F, Stošić-Grujičić S. Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology. 2013;262(1-2):72-78.
doi:10.1016/j.jneuroim.2013.07.001 .

Saksida, Tamara, Miljković, Djordje, Timotijević, Gordana, Stojanović, Ivana, Mijatović, Sanja, Fagone, Paolo, Mangano, Katia, Mammana, Santa, Farina, Claudio, Ascione, Ester, Maiello, Valentina, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis" in Journal of Neuroimmunology, 262, no. 1-2 (2013):72-78,
https://doi.org/10.1016/j.jneuroim.2013.07.001 . .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Stošić-Grujičić, Stanislava
AU  - Timotijević, Gordana
AU  - Sandler, Stellan
AU  - Stojanović, Ivana
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/552
AB  - As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity-associated type 2 diabetes (T2D). One potentially deleterious molecule for beta-cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta-cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondria! membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. Immunology and Cell Biology (2012) 90, 688-698; doi:10.1038/icb.2011.89; published online 8 November 2011
PB  - Wiley, Hoboken
T2  - Immunology and Cell Biology
T1  - Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis
EP  - 698
IS  - 7
SP  - 688
VL  - 90
DO  - 10.1038/icb.2011.89
ER  - 

@article{
author = "Saksida, Tamara and Stošić-Grujičić, Stanislava and Timotijević, Gordana and Sandler, Stellan and Stojanović, Ivana",
year = "2012",
abstract = "As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity-associated type 2 diabetes (T2D). One potentially deleterious molecule for beta-cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high-fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta-cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondria! membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. Immunology and Cell Biology (2012) 90, 688-698; doi:10.1038/icb.2011.89; published online 8 November 2011",
publisher = "Wiley, Hoboken",
journal = "Immunology and Cell Biology",
title = "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis",
pages = "698-688",
number = "7",
volume = "90",
doi = "10.1038/icb.2011.89"
}

Saksida, T., Stošić-Grujičić, S., Timotijević, G., Sandler, S.,& Stojanović, I.. (2012). Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology
Wiley, Hoboken., 90(7), 688-698.
https://doi.org/10.1038/icb.2011.89

Saksida T, Stošić-Grujičić S, Timotijević G, Sandler S, Stojanović I. Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. in Immunology and Cell Biology. 2012;90(7):688-698.
doi:10.1038/icb.2011.89 .

Saksida, Tamara, Stošić-Grujičić, Stanislava, Timotijević, Gordana, Sandler, Stellan, Stojanović, Ivana, "Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis" in Immunology and Cell Biology, 90, no. 7 (2012):688-698,
https://doi.org/10.1038/icb.2011.89 . .

TY  - JOUR
AU  - Stojanović, Ivana
AU  - Saksida, Tamara
AU  - Timotijević, Gordana
AU  - Sandler, Stellan
AU  - Stošić-Grujičić, Stanislava
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/599
AB  - Although several reports suggest a potentially deleterious role of macrophage migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim of the present study was to evaluate MIF effects on murine beta cells in the in vitro settings mimicking T2D-associated conditions. Results indicate that recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells upon exposure to palmitic acid or glucose. This was accompanied by upregulation of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content, and depolarized mitochondrial membrane. The final outcome was potentiation of mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be beneficial for maintaining integrity of endocrine pancreas in obesity-associated T2D.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Growth Factors
T1  - Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro
EP  - 393
IS  - 6
SP  - 385
VL  - 30
DO  - 10.3109/08977194.2012.734506
ER  - 

@article{
author = "Stojanović, Ivana and Saksida, Tamara and Timotijević, Gordana and Sandler, Stellan and Stošić-Grujičić, Stanislava",
year = "2012",
abstract = "Although several reports suggest a potentially deleterious role of macrophage migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim of the present study was to evaluate MIF effects on murine beta cells in the in vitro settings mimicking T2D-associated conditions. Results indicate that recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells upon exposure to palmitic acid or glucose. This was accompanied by upregulation of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content, and depolarized mitochondrial membrane. The final outcome was potentiation of mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be beneficial for maintaining integrity of endocrine pancreas in obesity-associated T2D.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Growth Factors",
title = "Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro",
pages = "393-385",
number = "6",
volume = "30",
doi = "10.3109/08977194.2012.734506"
}

Stojanović, I., Saksida, T., Timotijević, G., Sandler, S.,& Stošić-Grujičić, S.. (2012). Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro. in Growth Factors
Taylor & Francis Ltd, Abingdon., 30(6), 385-393.
https://doi.org/10.3109/08977194.2012.734506

Stojanović I, Saksida T, Timotijević G, Sandler S, Stošić-Grujičić S. Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro. in Growth Factors. 2012;30(6):385-393.
doi:10.3109/08977194.2012.734506 .

Stojanović, Ivana, Saksida, Tamara, Timotijević, Gordana, Sandler, Stellan, Stošić-Grujičić, Stanislava, "Macrophage migration inhibitory factor (MIF) enhances palmitic acid-and glucose-induced murine beta cell dysfunction and destruction in vitro" in Growth Factors, 30, no. 6 (2012):385-393,
https://doi.org/10.3109/08977194.2012.734506 . .

TY  - JOUR
AU  - Cvjeticanin, Tamara
AU  - Stojanović, Ivana
AU  - Timotijević, Gordana
AU  - Stošić-Grujičić, Stanislava
AU  - Miljković, Djordje
PY  - 2009
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/348
AB  - Background: Diabetes is characterized by progressive failure of insulin producing beta cells. It is well known that both saturated fatty acids and various products of immune cells can contribute to the reduction of beta cell viability and functionality during diabetes pathogenesis. However, their joint action on beta cells has not been investigated, so far. Therefore, we explored the possibility that leukocytes and saturated fatty acids cooperate in beta cell destruction. Results: Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells (LNC), or they were treated with cell-free supernatants (Sn) obtained from ConA-stimulated spleen cells or from activated CD3(+) cells, in the absence or presence of palmitic acid (PA). ConA-stimulated LNC or Sn and PA cooperated in inducing caspase-3-dependent RIN cell apoptosis. The observed effect of PA and Sn on RIN cell viability was mediated by p38 mitogen-activated protein kinase (MAPK)-signaling and was achieved through auto-destructive nitric oxide (NO) production. The cooperative effect of Sn was mimicked with the combination of interleukin-1 beta, interleukin-2, interleukin-6, interleukin-17, interferon-gamma and tumor necrosis factor-alpha. Conclusion: These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis.
PB  - BMC, London
T2  - BMC Immunology
T1  - T cells cooperate with palmitic acid in induction of beta cell apoptosis
VL  - 10
DO  - 10.1186/1471-2172-10-29
ER  - 

@article{
author = "Cvjeticanin, Tamara and Stojanović, Ivana and Timotijević, Gordana and Stošić-Grujičić, Stanislava and Miljković, Djordje",
year = "2009",
abstract = "Background: Diabetes is characterized by progressive failure of insulin producing beta cells. It is well known that both saturated fatty acids and various products of immune cells can contribute to the reduction of beta cell viability and functionality during diabetes pathogenesis. However, their joint action on beta cells has not been investigated, so far. Therefore, we explored the possibility that leukocytes and saturated fatty acids cooperate in beta cell destruction. Results: Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells (LNC), or they were treated with cell-free supernatants (Sn) obtained from ConA-stimulated spleen cells or from activated CD3(+) cells, in the absence or presence of palmitic acid (PA). ConA-stimulated LNC or Sn and PA cooperated in inducing caspase-3-dependent RIN cell apoptosis. The observed effect of PA and Sn on RIN cell viability was mediated by p38 mitogen-activated protein kinase (MAPK)-signaling and was achieved through auto-destructive nitric oxide (NO) production. The cooperative effect of Sn was mimicked with the combination of interleukin-1 beta, interleukin-2, interleukin-6, interleukin-17, interferon-gamma and tumor necrosis factor-alpha. Conclusion: These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis.",
publisher = "BMC, London",
journal = "BMC Immunology",
title = "T cells cooperate with palmitic acid in induction of beta cell apoptosis",
volume = "10",
doi = "10.1186/1471-2172-10-29"
}

Cvjeticanin, T., Stojanović, I., Timotijević, G., Stošić-Grujičić, S.,& Miljković, D.. (2009). T cells cooperate with palmitic acid in induction of beta cell apoptosis. in BMC Immunology
BMC, London., 10.
https://doi.org/10.1186/1471-2172-10-29

Cvjeticanin T, Stojanović I, Timotijević G, Stošić-Grujičić S, Miljković D. T cells cooperate with palmitic acid in induction of beta cell apoptosis. in BMC Immunology. 2009;10.
doi:10.1186/1471-2172-10-29 .

Cvjeticanin, Tamara, Stojanović, Ivana, Timotijević, Gordana, Stošić-Grujičić, Stanislava, Miljković, Djordje, "T cells cooperate with palmitic acid in induction of beta cell apoptosis" in BMC Immunology, 10 (2009),
https://doi.org/10.1186/1471-2172-10-29 . .