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 . .