Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes
Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease that selectively destroys pancreatic β cells. The only possible cure for T1DM is to control autoimmunity against β cell-specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activit...
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| Formato: | JOUR |
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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00099104_v177_n1_p149_Castro |
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todo:paper_00099104_v177_n1_p149_Castro |
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dspace |
| institution |
Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Dendritic cells Inflammation NOD mouse T lymphocytes T-bet curcumin cyclophosphamide cytokine gamma interferon immunoglobulin enhancer binding protein insulin nitric oxide T lymphocyte receptor transcription factor T bet adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell antigen specificity article autoimmunity cell activity cell death cell infiltration cell protection cellular immunity controlled study cytokine production cytokine release dendritic cell diabetogenesis disease course down regulation ex vivo study experimental diabetes mellitus female immunocompetent cell immunomodulation in vitro study insulin dependent diabetes mellitus insulitis leukocyte long term care lymphocyte proliferation mouse NOD SCID mouse nonhuman nonobese diabetic mouse outcome assessment pancreas islet beta cell pathogenesis population priority journal protein expression spleen cell T lymphocyte T lymphocyte activation Th1 cell transcription regulation translation regulation dendritic cells inflammation NOD mouse T lymphocytes T-bet Animals Anti-Inflammatory Agents, Non-Steroidal Antigen Presentation Antioxidants Cells, Cultured Curcumin Dendritic Cells Diabetes Mellitus, Experimental Diabetes Mellitus, Type 1 Disease Models, Animal Humans Interferon-gamma Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic NF-kappa B T-Box Domain Proteins Th1 Cells Transcriptional Activation |
| spellingShingle |
Dendritic cells Inflammation NOD mouse T lymphocytes T-bet curcumin cyclophosphamide cytokine gamma interferon immunoglobulin enhancer binding protein insulin nitric oxide T lymphocyte receptor transcription factor T bet adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell antigen specificity article autoimmunity cell activity cell death cell infiltration cell protection cellular immunity controlled study cytokine production cytokine release dendritic cell diabetogenesis disease course down regulation ex vivo study experimental diabetes mellitus female immunocompetent cell immunomodulation in vitro study insulin dependent diabetes mellitus insulitis leukocyte long term care lymphocyte proliferation mouse NOD SCID mouse nonhuman nonobese diabetic mouse outcome assessment pancreas islet beta cell pathogenesis population priority journal protein expression spleen cell T lymphocyte T lymphocyte activation Th1 cell transcription regulation translation regulation dendritic cells inflammation NOD mouse T lymphocytes T-bet Animals Anti-Inflammatory Agents, Non-Steroidal Antigen Presentation Antioxidants Cells, Cultured Curcumin Dendritic Cells Diabetes Mellitus, Experimental Diabetes Mellitus, Type 1 Disease Models, Animal Humans Interferon-gamma Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic NF-kappa B T-Box Domain Proteins Th1 Cells Transcriptional Activation Castro, C.N. Barcala Tabarrozzi, A.E. Winnewisser, J. Gimeno, M.L. Antunica Noguerol, M. Liberman, A.C. Paz, D.A. Dewey, R.A. Perone, M.J. Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes |
| topic_facet |
Dendritic cells Inflammation NOD mouse T lymphocytes T-bet curcumin cyclophosphamide cytokine gamma interferon immunoglobulin enhancer binding protein insulin nitric oxide T lymphocyte receptor transcription factor T bet adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell antigen specificity article autoimmunity cell activity cell death cell infiltration cell protection cellular immunity controlled study cytokine production cytokine release dendritic cell diabetogenesis disease course down regulation ex vivo study experimental diabetes mellitus female immunocompetent cell immunomodulation in vitro study insulin dependent diabetes mellitus insulitis leukocyte long term care lymphocyte proliferation mouse NOD SCID mouse nonhuman nonobese diabetic mouse outcome assessment pancreas islet beta cell pathogenesis population priority journal protein expression spleen cell T lymphocyte T lymphocyte activation Th1 cell transcription regulation translation regulation dendritic cells inflammation NOD mouse T lymphocytes T-bet Animals Anti-Inflammatory Agents, Non-Steroidal Antigen Presentation Antioxidants Cells, Cultured Curcumin Dendritic Cells Diabetes Mellitus, Experimental Diabetes Mellitus, Type 1 Disease Models, Animal Humans Interferon-gamma Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic NF-kappa B T-Box Domain Proteins Th1 Cells Transcriptional Activation |
| description |
Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease that selectively destroys pancreatic β cells. The only possible cure for T1DM is to control autoimmunity against β cell-specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activities, might down-regulate the T cell response that destroys pancreatic β cells to improve disease outcome in autoimmune diabetes. We employed two accelerated autoimmune diabetes models: (i) cyclophosphamide (CYP) administration to non-obese diabetic (NOD) mice and (ii) adoptive transfer of diabetogenic splenocytes into NODscid mice. Curcumin treatment led to significant delay of disease onset, and in some instances prevented autoimmune diabetes by inhibiting pancreatic leucocyte infiltration and preserving insulin-expressing cells. To investigate the mechanisms of protection we studied the effect of curcumin on key immune cell populations involved in the pathogenesis of the disease. Curcumin modulates the T lymphocyte response impairing proliferation and interferon (IFN)-γ production through modulation of T-box expressed in T cells (T-bet), a key transcription factor for proinflammatory T helper type 1 (Th1) lymphocyte differentiation, both at the transcriptional and translational levels. Also, curcumin reduces nuclear factor (NF)-κB activation in T cell receptor (TCR)-stimulated NOD lymphocytes. In addition, curcumin impairs the T cell stimulatory function of dendritic cells with reduced secretion of proinflammatory cytokines and nitric oxide (NO) and low surface expression of co-stimulatory molecules, leading to an overall diminished antigen-presenting cell activity. These in-vitro effects correlated with ex-vivo analysis of cells obtained from curcumin-treated mice during the course of autoimmune diabetes. These findings reveal an effective therapeutic effect of curcumin in autoimmune diabetes by its actions on key immune cells responsible for β cell death. © 2014 British Society for Immunology. |
| format |
JOUR |
| author |
Castro, C.N. Barcala Tabarrozzi, A.E. Winnewisser, J. Gimeno, M.L. Antunica Noguerol, M. Liberman, A.C. Paz, D.A. Dewey, R.A. Perone, M.J. |
| author_facet |
Castro, C.N. Barcala Tabarrozzi, A.E. Winnewisser, J. Gimeno, M.L. Antunica Noguerol, M. Liberman, A.C. Paz, D.A. Dewey, R.A. Perone, M.J. |
| author_sort |
Castro, C.N. |
| title |
Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes |
| title_short |
Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes |
| title_full |
Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes |
| title_fullStr |
Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes |
| title_full_unstemmed |
Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes |
| title_sort |
curcumin ameliorates autoimmune diabetes. evidence in accelerated murine models of type 1 diabetes |
| url |
http://hdl.handle.net/20.500.12110/paper_00099104_v177_n1_p149_Castro |
| work_keys_str_mv |
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1807318311105462272 |
| spelling |
todo:paper_00099104_v177_n1_p149_Castro2023-10-03T14:08:49Z Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes Castro, C.N. Barcala Tabarrozzi, A.E. Winnewisser, J. Gimeno, M.L. Antunica Noguerol, M. Liberman, A.C. Paz, D.A. Dewey, R.A. Perone, M.J. Dendritic cells Inflammation NOD mouse T lymphocytes T-bet curcumin cyclophosphamide cytokine gamma interferon immunoglobulin enhancer binding protein insulin nitric oxide T lymphocyte receptor transcription factor T bet adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell antigen specificity article autoimmunity cell activity cell death cell infiltration cell protection cellular immunity controlled study cytokine production cytokine release dendritic cell diabetogenesis disease course down regulation ex vivo study experimental diabetes mellitus female immunocompetent cell immunomodulation in vitro study insulin dependent diabetes mellitus insulitis leukocyte long term care lymphocyte proliferation mouse NOD SCID mouse nonhuman nonobese diabetic mouse outcome assessment pancreas islet beta cell pathogenesis population priority journal protein expression spleen cell T lymphocyte T lymphocyte activation Th1 cell transcription regulation translation regulation dendritic cells inflammation NOD mouse T lymphocytes T-bet Animals Anti-Inflammatory Agents, Non-Steroidal Antigen Presentation Antioxidants Cells, Cultured Curcumin Dendritic Cells Diabetes Mellitus, Experimental Diabetes Mellitus, Type 1 Disease Models, Animal Humans Interferon-gamma Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic NF-kappa B T-Box Domain Proteins Th1 Cells Transcriptional Activation Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease that selectively destroys pancreatic β cells. The only possible cure for T1DM is to control autoimmunity against β cell-specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activities, might down-regulate the T cell response that destroys pancreatic β cells to improve disease outcome in autoimmune diabetes. We employed two accelerated autoimmune diabetes models: (i) cyclophosphamide (CYP) administration to non-obese diabetic (NOD) mice and (ii) adoptive transfer of diabetogenic splenocytes into NODscid mice. Curcumin treatment led to significant delay of disease onset, and in some instances prevented autoimmune diabetes by inhibiting pancreatic leucocyte infiltration and preserving insulin-expressing cells. To investigate the mechanisms of protection we studied the effect of curcumin on key immune cell populations involved in the pathogenesis of the disease. Curcumin modulates the T lymphocyte response impairing proliferation and interferon (IFN)-γ production through modulation of T-box expressed in T cells (T-bet), a key transcription factor for proinflammatory T helper type 1 (Th1) lymphocyte differentiation, both at the transcriptional and translational levels. Also, curcumin reduces nuclear factor (NF)-κB activation in T cell receptor (TCR)-stimulated NOD lymphocytes. In addition, curcumin impairs the T cell stimulatory function of dendritic cells with reduced secretion of proinflammatory cytokines and nitric oxide (NO) and low surface expression of co-stimulatory molecules, leading to an overall diminished antigen-presenting cell activity. These in-vitro effects correlated with ex-vivo analysis of cells obtained from curcumin-treated mice during the course of autoimmune diabetes. These findings reveal an effective therapeutic effect of curcumin in autoimmune diabetes by its actions on key immune cells responsible for β cell death. © 2014 British Society for Immunology. Fil:Castro, C.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Liberman, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Paz, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00099104_v177_n1_p149_Castro |