Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage
Нема приказа
Аутори
Volarevic, VladislavPaunović, Verica G.
Marković, Zoran M.
Marković-Simović, Bojana
Misirkić-Marjanović, Maja
Todorović-Marković, Biljana
Bojic, Sanja
Vucicevic, Ljubica
Jovanović, Svetlana P.
Arsenijević, Nebojša N.
Holclajtner-Antunović, Ivanka D.
Milosavljević, Momir
Dramićanin, Miroslav
Kravić-Stevović, Tamara K.
Ćirić, Darko
Lukić, Miodrag L.
Trajković, Vladimir S.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
We investigated the effect of large (40 nm) graphene quantum dots (GQDs) in concanavalin A (Con A; 12 mg/kg i.v.)-induced mouse hepatitis, a T cell-mediated liver injury resembling fulminant hepatitis in humans. Intravenously injected GQDs (50 mg/kg) accumulated in liver and reduced Con A-mediated liver damage, as demonstrated by histopathological analysis and a decrease in liver lipid peroxidation and serum levels of liver transaminases. The cleavage of apoptotic markers caspase-3/PARP and mRNA levels of proapoptotic mediators Puma, Noxa, Bax, Bak1, Bim, Apaf1, and p21, as well as LC3-I conversion to autophagosome-associated LC3-II and expression of autophagy-related (Atg) genes Atg4b, Atg7, Atg12, and beclin-1, were attenuated by GQDs, indicating a decrease in both apoptosis and autophagy in the liver tissue. This was associated with the reduced liver infiltration of immune cells, particularly the T cells producing proinflammatory cytokine IFN-?, and a decrease in IFN-gamma serum lev...els. In the spleen of GQD-exposed mice, mRNA expression of IFN-? and its transcription factor T-bet was reduced, while that of the IL-33 ligand ST2 was increased. The hepatoprotective effect of GQDs was less pronounced in ST2-deficient mice, indicating that it might depend on ST2 upregulation. In vitro, GQDs inhibited splenocyte IFN-gamma production, reduced the activation of extracellular signal-regulated kinase in macrophage and T cell lines, inhibited macrophage production of the free radical nitric oxide, and reduced its cytotoxicity toward hepatocyte cell line HepG2. Therefore, GQDs alleviate immune-mediated fulminant hepatitis by interfering with T cell and macrophage activation and possibly by exerting a direct hepatoprotective effect.
Кључне речи:
graphene / quantum dot / hepatitis / apoptosis / autophagyИзвор:
ACS Nano, 2014, 8, 12, 12098-12109Финансирање / пројекти:
- Модулација сигналних путева који контролишу интрацелуларни енергетски баланс у терапији тумора и неуро-имуно-ендокриних поремећаја (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
- Молекулске детерминанте урођене имуности у аутоимунским болестима и канцерогенези (RS-MESTD-Basic Research (BR or ON)-175069)
- Развој инфраструктуре за приоритетна поља науке (RS-MESTD-Basic Research (BR or ON)-175103)
- Faculty of Medical Sciences University of Kragujevac, Serbia [MP01/12]
DOI: 10.1021/nn502466z
ISSN: 1936-0851; 1936-086X
PubMed: 25415137
WoS: 000347138000023
Scopus: 2-s2.0-84919725926
Колекције
Институција/група
VinčaTY - JOUR AU - Volarevic, Vladislav AU - Paunović, Verica G. AU - Marković, Zoran M. AU - Marković-Simović, Bojana AU - Misirkić-Marjanović, Maja AU - Todorović-Marković, Biljana AU - Bojic, Sanja AU - Vucicevic, Ljubica AU - Jovanović, Svetlana P. AU - Arsenijević, Nebojša N. AU - Holclajtner-Antunović, Ivanka D. AU - Milosavljević, Momir AU - Dramićanin, Miroslav AU - Kravić-Stevović, Tamara K. AU - Ćirić, Darko AU - Lukić, Miodrag L. AU - Trajković, Vladimir S. PY - 2014 UR - https://vinar.vin.bg.ac.rs/handle/123456789/324 AB - We investigated the effect of large (40 nm) graphene quantum dots (GQDs) in concanavalin A (Con A; 12 mg/kg i.v.)-induced mouse hepatitis, a T cell-mediated liver injury resembling fulminant hepatitis in humans. Intravenously injected GQDs (50 mg/kg) accumulated in liver and reduced Con A-mediated liver damage, as demonstrated by histopathological analysis and a decrease in liver lipid peroxidation and serum levels of liver transaminases. The cleavage of apoptotic markers caspase-3/PARP and mRNA levels of proapoptotic mediators Puma, Noxa, Bax, Bak1, Bim, Apaf1, and p21, as well as LC3-I conversion to autophagosome-associated LC3-II and expression of autophagy-related (Atg) genes Atg4b, Atg7, Atg12, and beclin-1, were attenuated by GQDs, indicating a decrease in both apoptosis and autophagy in the liver tissue. This was associated with the reduced liver infiltration of immune cells, particularly the T cells producing proinflammatory cytokine IFN-?, and a decrease in IFN-gamma serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-? and its transcription factor T-bet was reduced, while that of the IL-33 ligand ST2 was increased. The hepatoprotective effect of GQDs was less pronounced in ST2-deficient mice, indicating that it might depend on ST2 upregulation. In vitro, GQDs inhibited splenocyte IFN-gamma production, reduced the activation of extracellular signal-regulated kinase in macrophage and T cell lines, inhibited macrophage production of the free radical nitric oxide, and reduced its cytotoxicity toward hepatocyte cell line HepG2. Therefore, GQDs alleviate immune-mediated fulminant hepatitis by interfering with T cell and macrophage activation and possibly by exerting a direct hepatoprotective effect. T2 - ACS Nano T1 - Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage VL - 8 IS - 12 SP - 12098 EP - 12109 DO - 10.1021/nn502466z ER -
@article{ author = "Volarevic, Vladislav and Paunović, Verica G. and Marković, Zoran M. and Marković-Simović, Bojana and Misirkić-Marjanović, Maja and Todorović-Marković, Biljana and Bojic, Sanja and Vucicevic, Ljubica and Jovanović, Svetlana P. and Arsenijević, Nebojša N. and Holclajtner-Antunović, Ivanka D. and Milosavljević, Momir and Dramićanin, Miroslav and Kravić-Stevović, Tamara K. and Ćirić, Darko and Lukić, Miodrag L. and Trajković, Vladimir S.", year = "2014", abstract = "We investigated the effect of large (40 nm) graphene quantum dots (GQDs) in concanavalin A (Con A; 12 mg/kg i.v.)-induced mouse hepatitis, a T cell-mediated liver injury resembling fulminant hepatitis in humans. Intravenously injected GQDs (50 mg/kg) accumulated in liver and reduced Con A-mediated liver damage, as demonstrated by histopathological analysis and a decrease in liver lipid peroxidation and serum levels of liver transaminases. The cleavage of apoptotic markers caspase-3/PARP and mRNA levels of proapoptotic mediators Puma, Noxa, Bax, Bak1, Bim, Apaf1, and p21, as well as LC3-I conversion to autophagosome-associated LC3-II and expression of autophagy-related (Atg) genes Atg4b, Atg7, Atg12, and beclin-1, were attenuated by GQDs, indicating a decrease in both apoptosis and autophagy in the liver tissue. This was associated with the reduced liver infiltration of immune cells, particularly the T cells producing proinflammatory cytokine IFN-?, and a decrease in IFN-gamma serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-? and its transcription factor T-bet was reduced, while that of the IL-33 ligand ST2 was increased. The hepatoprotective effect of GQDs was less pronounced in ST2-deficient mice, indicating that it might depend on ST2 upregulation. In vitro, GQDs inhibited splenocyte IFN-gamma production, reduced the activation of extracellular signal-regulated kinase in macrophage and T cell lines, inhibited macrophage production of the free radical nitric oxide, and reduced its cytotoxicity toward hepatocyte cell line HepG2. Therefore, GQDs alleviate immune-mediated fulminant hepatitis by interfering with T cell and macrophage activation and possibly by exerting a direct hepatoprotective effect.", journal = "ACS Nano", title = "Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage", volume = "8", number = "12", pages = "12098-12109", doi = "10.1021/nn502466z" }
Volarevic, V., Paunović, V. G., Marković, Z. M., Marković-Simović, B., Misirkić-Marjanović, M., Todorović-Marković, B., Bojic, S., Vucicevic, L., Jovanović, S. P., Arsenijević, N. N., Holclajtner-Antunović, I. D., Milosavljević, M., Dramićanin, M., Kravić-Stevović, T. K., Ćirić, D., Lukić, M. L.,& Trajković, V. S.. (2014). Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage. in ACS Nano, 8(12), 12098-12109. https://doi.org/10.1021/nn502466z
Volarevic V, Paunović VG, Marković ZM, Marković-Simović B, Misirkić-Marjanović M, Todorović-Marković B, Bojic S, Vucicevic L, Jovanović SP, Arsenijević NN, Holclajtner-Antunović ID, Milosavljević M, Dramićanin M, Kravić-Stevović TK, Ćirić D, Lukić ML, Trajković VS. Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage. in ACS Nano. 2014;8(12):12098-12109. doi:10.1021/nn502466z .
Volarevic, Vladislav, Paunović, Verica G., Marković, Zoran M., Marković-Simović, Bojana, Misirkić-Marjanović, Maja, Todorović-Marković, Biljana, Bojic, Sanja, Vucicevic, Ljubica, Jovanović, Svetlana P., Arsenijević, Nebojša N., Holclajtner-Antunović, Ivanka D., Milosavljević, Momir, Dramićanin, Miroslav, Kravić-Stevović, Tamara K., Ćirić, Darko, Lukić, Miodrag L., Trajković, Vladimir S., "Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage" in ACS Nano, 8, no. 12 (2014):12098-12109, https://doi.org/10.1021/nn502466z . .