TY  - JOUR
AU  - Protić-Rosić, Isidora
AU  - Nešić, Andrijana
AU  - Lukić, Ivana
AU  - Miljković, Radmila
AU  - Popović, Dragan M.
AU  - Atanasković-Marković, Marina
AU  - Stojanović, Marijana
AU  - Gavrović -Jankulović, Marija
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4777
AB  - Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.
PB  - Elsevier
T2  - Molecular Immunology
T1  - Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion
VL  - 138
SP  - 58
EP  - 67
DO  - 10.1016/j.molimm.2021.06.015
ER  - 

@article{
author = "Protić-Rosić, Isidora and Nešić, Andrijana and Lukić, Ivana and Miljković, Radmila and Popović, Dragan M. and Atanasković-Marković, Marina and Stojanović, Marijana and Gavrović -Jankulović, Marija",
year = "2021",
abstract = "Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.",
publisher = "Elsevier",
journal = "Molecular Immunology",
title = "Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion",
volume = "138",
pages = "58-67",
doi = "10.1016/j.molimm.2021.06.015"
}

Protić-Rosić, I., Nešić, A., Lukić, I., Miljković, R., Popović, D. M., Atanasković-Marković, M., Stojanović, M.,& Gavrović -Jankulović, M.. (2021). Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion. in Molecular Immunology
Elsevier., 138, 58-67.
https://doi.org/10.1016/j.molimm.2021.06.015

Protić-Rosić I, Nešić A, Lukić I, Miljković R, Popović DM, Atanasković-Marković M, Stojanović M, Gavrović -Jankulović M. Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion. in Molecular Immunology. 2021;138:58-67.
doi:10.1016/j.molimm.2021.06.015 .

Protić-Rosić, Isidora, Nešić, Andrijana, Lukić, Ivana, Miljković, Radmila, Popović, Dragan M., Atanasković-Marković, Marina, Stojanović, Marijana, Gavrović -Jankulović, Marija, "Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion" in Molecular Immunology, 138 (2021):58-67,
https://doi.org/10.1016/j.molimm.2021.06.015 . .

TY  - JOUR
AU  - Nikolić, Jasna
AU  - Nešić, Andrijana
AU  - Čavić, Milena
AU  - Đorđević, Neda O.
AU  - Anđelković, Uroš
AU  - Atanasković-Marković, Marina
AU  - Drakulić, Branko
AU  - Gavrović-Jankulović, Marija
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2058
AB  - Background: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity.
PB  - Elsevier
T2  - Biochimica et Biophysica Acta-General Subjects
T1  - Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells
VL  - 1861
IS  - 2
SP  - 126
EP  - 134
DO  - 10.1016/j.bbagen.2016.11.021
ER  - 

@article{
author = "Nikolić, Jasna and Nešić, Andrijana and Čavić, Milena and Đorđević, Neda O. and Anđelković, Uroš and Atanasković-Marković, Marina and Drakulić, Branko and Gavrović-Jankulović, Marija",
year = "2017",
abstract = "Background: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity.",
publisher = "Elsevier",
journal = "Biochimica et Biophysica Acta-General Subjects",
title = "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells",
volume = "1861",
number = "2",
pages = "126-134",
doi = "10.1016/j.bbagen.2016.11.021"
}

Nikolić, J., Nešić, A., Čavić, M., Đorđević, N. O., Anđelković, U., Atanasković-Marković, M., Drakulić, B.,& Gavrović-Jankulović, M.. (2017). Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta-General Subjects
Elsevier., 1861(2), 126-134.
https://doi.org/10.1016/j.bbagen.2016.11.021

Nikolić J, Nešić A, Čavić M, Đorđević NO, Anđelković U, Atanasković-Marković M, Drakulić B, Gavrović-Jankulović M. Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta-General Subjects. 2017;1861(2):126-134.
doi:10.1016/j.bbagen.2016.11.021 .

Nikolić, Jasna, Nešić, Andrijana, Čavić, Milena, Đorđević, Neda O., Anđelković, Uroš, Atanasković-Marković, Marina, Drakulić, Branko, Gavrović-Jankulović, Marija, "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells" in Biochimica et Biophysica Acta-General Subjects, 1861, no. 2 (2017):126-134,
https://doi.org/10.1016/j.bbagen.2016.11.021 . .

TY  - JOUR
AU  - Nikolić, Jasna
AU  - Nešić, Andrijana
AU  - Čavić, Milena
AU  - Đorđević, Neda O.
AU  - Anđelković, Uroš
AU  - Atanasković-Marković, Marina
AU  - Drakulić, Branko
AU  - Gavrović-Jankulović, Marija
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3042
AB  - Background: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity.
PB  - Elsevier
T2  - Biochimica et Biophysica Acta-General Subjects
T1  - Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells
VL  - 1861
IS  - 2
SP  - 126
EP  - 134
DO  - 10.1016/j.bbagen.2016.11.021
ER  - 

@article{
author = "Nikolić, Jasna and Nešić, Andrijana and Čavić, Milena and Đorđević, Neda O. and Anđelković, Uroš and Atanasković-Marković, Marina and Drakulić, Branko and Gavrović-Jankulović, Marija",
year = "2017",
abstract = "Background: Protein oxidation can occur as a consequence of lipid peroxidation during food processing. The aim of this work was to explore the effect of malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84 intestinal cells. Methods: Molecular dynamics simulation was employed for the prediction of MDA modification in the OVA, while introduced structural changes were evaluated by measurement of carbonyl group content, fluorescence spectra, MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial cells were analyzed by gene expression for pro-inflammatory cytokines and protein secretion. Results: Out of 9 predicted, five modified Lys residues were confirmed by MS/MS analysis: (51)TQINKVVR(58), (85)DILNQITKPNDVYSFSLASR(104), (111)YPILPEYLQCVKELYR(126), (187)AFKDEDTQAMPFR(99), (KIKVYLPR284)-K-277, and (IKVYLPR284)-I-278. The introduced MDA modifications influenced profile of IgE reactivity to OVA. Treatment of T84 epithelial cells with OVA and OVA modified with 1 mM MDA, induced up-regulation of pro-inflammatory cytokines (IL-1 beta,IL-25, IL-33, TSLP and TNF alpha), while OVA modification with 10 mM MDA induced down regulation of the cytokine expression profile, except for IL-1 beta. OVA and OVA modified with 1 mM MDA induced secretion of epithelial cells specific cytokine IL-33. Conclusions: This finding indicated that OVA and its MDA modified form have the potential to trigger the innate immunity by inducing up-regulation and secretion of pro-allergenic IL-33 in T84 intestinal epithelial cells. General significance: Interactions of ovalbumin and its MDA modified form with intestinal epithelial cells can induce a specific immunological priming necessary for the downstream activation of innate immunity.",
publisher = "Elsevier",
journal = "Biochimica et Biophysica Acta-General Subjects",
title = "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells",
volume = "1861",
number = "2",
pages = "126-134",
doi = "10.1016/j.bbagen.2016.11.021"
}

Nikolić, J., Nešić, A., Čavić, M., Đorđević, N. O., Anđelković, U., Atanasković-Marković, M., Drakulić, B.,& Gavrović-Jankulović, M.. (2017). Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta-General Subjects
Elsevier., 1861(2), 126-134.
https://doi.org/10.1016/j.bbagen.2016.11.021

Nikolić J, Nešić A, Čavić M, Đorđević NO, Anđelković U, Atanasković-Marković M, Drakulić B, Gavrović-Jankulović M. Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells. in Biochimica et Biophysica Acta-General Subjects. 2017;1861(2):126-134.
doi:10.1016/j.bbagen.2016.11.021 .

Nikolić, Jasna, Nešić, Andrijana, Čavić, Milena, Đorđević, Neda O., Anđelković, Uroš, Atanasković-Marković, Marina, Drakulić, Branko, Gavrović-Jankulović, Marija, "Effect of malondialdehyde on the ovalbumin structure and its interactions with T84 epithelial cells" in Biochimica et Biophysica Acta-General Subjects, 1861, no. 2 (2017):126-134,
https://doi.org/10.1016/j.bbagen.2016.11.021 . .

TY  - JOUR
AU  - Grozdanović, Milica
AU  - Čavić, Milena
AU  - Nešić, Andrijana
AU  - Anđelković, Uroš
AU  - Akbari, Peyman
AU  - Smit, Joost J.
AU  - Gavrović-Jankulović, Marija
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3154
AB  - Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions
VL  - 1860
IS  - 3
SP  - 516
EP  - 526
DO  - 10.1016/j.bbagen.2015.12.005
ER  - 

@article{
author = "Grozdanović, Milica and Čavić, Milena and Nešić, Andrijana and Anđelković, Uroš and Akbari, Peyman and Smit, Joost J. and Gavrović-Jankulović, Marija",
year = "2016",
abstract = "Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions",
volume = "1860",
number = "3",
pages = "516-526",
doi = "10.1016/j.bbagen.2015.12.005"
}

Grozdanović, M., Čavić, M., Nešić, A., Anđelković, U., Akbari, P., Smit, J. J.,& Gavrović-Jankulović, M.. (2016). Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects
Elsevier., 1860(3), 516-526.
https://doi.org/10.1016/j.bbagen.2015.12.005

Grozdanović M, Čavić M, Nešić A, Anđelković U, Akbari P, Smit JJ, Gavrović-Jankulović M. Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects. 2016;1860(3):516-526.
doi:10.1016/j.bbagen.2015.12.005 .

Grozdanović, Milica, Čavić, Milena, Nešić, Andrijana, Anđelković, Uroš, Akbari, Peyman, Smit, Joost J., Gavrović-Jankulović, Marija, "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions" in Biochimica et Biophysica Acta: General Subjects, 1860, no. 3 (2016):516-526,
https://doi.org/10.1016/j.bbagen.2015.12.005 . .

TY  - JOUR
AU  - Grozdanović, Milica
AU  - Čavić, Milena
AU  - Nešić, Andrijana
AU  - Anđelković, Uroš
AU  - Akbari, Peyman
AU  - Smit, Joost J.
AU  - Gavrović-Jankulović, Marija
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3155
AB  - Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.
PB  - Elsevier
T2  - Biochimica et Biophysica Acta: General Subjects
T1  - Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions
VL  - 1860
IS  - 3
SP  - 516
EP  - 526
DO  - 10.1016/j.bbagen.2015.12.005
ER  - 

@article{
author = "Grozdanović, Milica and Čavić, Milena and Nešić, Andrijana and Anđelković, Uroš and Akbari, Peyman and Smit, Joost J. and Gavrović-Jankulović, Marija",
year = "2016",
abstract = "Background: The intestinal epithelium forms a barrier that food allergens must cross in order to induce sensitization. The aim of this study was to evaluate the impact of the plant-derived food cysteine protease - actinidin (Act d1) on the integrity of intestinal epithelium tight junctions (TJs). Methods: Effects of Act d1 on the intestinal epithelium were evaluated in Caco-2 monolayers and in a mouse model by measuring transepithelial resistance and in vivo permeability. Integrity of the tight junctions was analyzed by confocal microscopy. Proteolysis of TJ protein occludin was evaluated by mass spectrometry. Results: Actinidin (1 mg/mL) reduced the transepithelial resistance of the cell monolayer by 18.1% (after 1 h) and 25.6% (after 4 h). This loss of barrier function was associated with Act d 1 disruption of the occludin and zonula occludens (ZO)-1 network. The effect on intestinal permeability in vivo was demonstrated by the significantly higher concentration of 40 kDa FITC-dextran (233 mu g/mL) that passed from the intestine into the serum of Act d1 treated mice in comparison to the control group (0.5 mu g/mL). Human occludin was fragmented, and putative Act d1 cleavage sites were identified in extracellular loops of human occludin. Conclusion: Act d1 caused protease-dependent disruption of tight junctions in confluent Caco-2 cells and increased intestinal permeability in mice. General significance: In line with the observed effects of food cysteine proteases in occupational allergy, these results suggest that disruption of tight junctions by food cysteine proteases may contribute to the process of sensitization in food allergy. (C) 2015 Elsevier B.V. All rights reserved.",
publisher = "Elsevier",
journal = "Biochimica et Biophysica Acta: General Subjects",
title = "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions",
volume = "1860",
number = "3",
pages = "516-526",
doi = "10.1016/j.bbagen.2015.12.005"
}

Grozdanović, M., Čavić, M., Nešić, A., Anđelković, U., Akbari, P., Smit, J. J.,& Gavrović-Jankulović, M.. (2016). Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects
Elsevier., 1860(3), 516-526.
https://doi.org/10.1016/j.bbagen.2015.12.005

Grozdanović M, Čavić M, Nešić A, Anđelković U, Akbari P, Smit JJ, Gavrović-Jankulović M. Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions. in Biochimica et Biophysica Acta: General Subjects. 2016;1860(3):516-526.
doi:10.1016/j.bbagen.2015.12.005 .

Grozdanović, Milica, Čavić, Milena, Nešić, Andrijana, Anđelković, Uroš, Akbari, Peyman, Smit, Joost J., Gavrović-Jankulović, Marija, "Kiwifruit cysteine protease actinidin compromises the intestinal barrier by disrupting tight junctions" in Biochimica et Biophysica Acta: General Subjects, 1860, no. 3 (2016):516-526,
https://doi.org/10.1016/j.bbagen.2015.12.005 . .