Large Graphene Quantum Dots Alleviate Immune-Mediated Liver Damage
No Thumbnail
Authors
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.
Article (Published version)
Metadata
Show full item recordAbstract
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.
Keywords:
graphene / quantum dot / hepatitis / apoptosis / autophagySource:
ACS Nano, 2014, 8, 12, 12098-12109Funding / projects:
- Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
- Molecular determinants of innate immunity in autoimmunity and tumorogenesis (RS-MESTD-Basic Research (BR or ON)-175069)
- Developing infrastructure for priority research fields (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
Collections
Institution/Community
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 . .