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Protective effects of carbonyl iron against multiple low‐dose streptozotocin‐induced diabetes in rodents

Particulate adjuvants have shown increasing promise as effective, safe, and durable agents for the stimulation of immunity, or alternatively, the suppression of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ‐specific autoimmune disease—typ...

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Published in:Journal of cellular physiology 2018-06, Vol.233 (6), p.4990-5001
Main Authors: Vujicic, Milica, Saksida, Tamara, Mostarica Stojkovic, Marija, Djedovic, Neda, Stojanovic, Ivana, Stosic‐Grujicic, Stanislava
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Saksida, Tamara
Mostarica Stojkovic, Marija
Djedovic, Neda
Stojanovic, Ivana
Stosic‐Grujicic, Stanislava
description Particulate adjuvants have shown increasing promise as effective, safe, and durable agents for the stimulation of immunity, or alternatively, the suppression of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ‐specific autoimmune disease—type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS‐treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia. The protective action was obtained either when CI was applied 7 days before, simultaneously with the first dose of streptozotocin, or 1 day after MLDS treatment. Ex vivo cell analysis of C57BL/6 mice showed that CI treatment reduced the proportion of proinflammatory F4/80+CD40+ M1 macrophages and activated T lymphocytes in the spleen. Moreover, the treatment down‐regulated the number of inflammatory CD4+IFN‐γ+ cells in pancreatic lymph nodes, Peyer's patches, and pancreas‐infiltrating mononuclear cells, while simultaneously potentiating proportion of CD4+IL17+ cells. The regulatory arm of the immune system represented by CD3+NK1.1+ (NKT) and CD4+CD25+FoxP3+ regulatory T cells was potentiated after CI treatment. In vitro analysis showed that CI down‐regulated CD40 and CD80 expression on dendritic cells thus probably interfering with their antigen‐presenting ability. In conclusion, particulate adjuvant CI seems to suppress the activation of the innate immune response, which further affects the adaptive immune response directed toward pancreatic beta cells. Carbonyl iron, a strong adjuvant, is able to prevent development of type 1 diabetes induced in mice and rats. It probably reduces the ability of antigen‐presenting cells to activate autoreactive T helper 1 cells that mediate destruction of pancreatic islets during diabetes progression.
doi_str_mv 10.1002/jcp.26338
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Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ‐specific autoimmune disease—type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS‐treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia. The protective action was obtained either when CI was applied 7 days before, simultaneously with the first dose of streptozotocin, or 1 day after MLDS treatment. Ex vivo cell analysis of C57BL/6 mice showed that CI treatment reduced the proportion of proinflammatory F4/80+CD40+ M1 macrophages and activated T lymphocytes in the spleen. Moreover, the treatment down‐regulated the number of inflammatory CD4+IFN‐γ+ cells in pancreatic lymph nodes, Peyer's patches, and pancreas‐infiltrating mononuclear cells, while simultaneously potentiating proportion of CD4+IL17+ cells. The regulatory arm of the immune system represented by CD3+NK1.1+ (NKT) and CD4+CD25+FoxP3+ regulatory T cells was potentiated after CI treatment. In vitro analysis showed that CI down‐regulated CD40 and CD80 expression on dendritic cells thus probably interfering with their antigen‐presenting ability. In conclusion, particulate adjuvant CI seems to suppress the activation of the innate immune response, which further affects the adaptive immune response directed toward pancreatic beta cells. Carbonyl iron, a strong adjuvant, is able to prevent development of type 1 diabetes induced in mice and rats. 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Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ‐specific autoimmune disease—type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS‐treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia. The protective action was obtained either when CI was applied 7 days before, simultaneously with the first dose of streptozotocin, or 1 day after MLDS treatment. Ex vivo cell analysis of C57BL/6 mice showed that CI treatment reduced the proportion of proinflammatory F4/80+CD40+ M1 macrophages and activated T lymphocytes in the spleen. Moreover, the treatment down‐regulated the number of inflammatory CD4+IFN‐γ+ cells in pancreatic lymph nodes, Peyer's patches, and pancreas‐infiltrating mononuclear cells, while simultaneously potentiating proportion of CD4+IL17+ cells. The regulatory arm of the immune system represented by CD3+NK1.1+ (NKT) and CD4+CD25+FoxP3+ regulatory T cells was potentiated after CI treatment. In vitro analysis showed that CI down‐regulated CD40 and CD80 expression on dendritic cells thus probably interfering with their antigen‐presenting ability. In conclusion, particulate adjuvant CI seems to suppress the activation of the innate immune response, which further affects the adaptive immune response directed toward pancreatic beta cells. Carbonyl iron, a strong adjuvant, is able to prevent development of type 1 diabetes induced in mice and rats. It probably reduces the ability of antigen‐presenting cells to activate autoreactive T helper 1 cells that mediate destruction of pancreatic islets during diabetes progression.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29215791</pmid><doi>10.1002/jcp.26338</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-8542-1327</orcidid></addata></record>
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1097-4652
language eng
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source Wiley-Blackwell Read & Publish Collection
subjects Adaptive immunity
adjuvant
Adjuvants
Adjuvants, Immunologic - pharmacology
Animals
Autoimmunity - drug effects
Beta cells
Carbonyl compounds
carbonyl iron
Carbonyls
CD25 antigen
CD3 antigen
CD4 antigen
CD40 antigen
CD80 antigen
Cell death
Cells, Cultured
Coculture Techniques
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - immunology
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Experimental - chemically induced
Diabetes Mellitus, Experimental - immunology
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Experimental - prevention & control
Diabetes Mellitus, Type 1 - chemically induced
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 1 - pathology
Diabetes Mellitus, Type 1 - prevention & control
Foxp3 protein
Hyperglycemia
Hypoglycemic Agents - pharmacology
Immune response
Immune system
Immunity
Immunity, Innate - drug effects
Immunoregulation
In vivo methods and tests
Infiltration
Inflammation
Innate immunity
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - immunology
Insulin-Secreting Cells - pathology
Insulitis
Interferon
Interleukin 1
Interleukin 17
Iron
Iron Compounds - pharmacology
Lymph nodes
Lymph Nodes - drug effects
Lymph Nodes - immunology
Lymphocyte Activation - drug effects
Lymphocytes
Lymphocytes T
Macrophage Activation - drug effects
Macrophages
Macrophages - drug effects
Macrophages - immunology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Pancreas
Peyer's patches
Peyer's Patches - drug effects
Peyer's Patches - immunology
Rats
Rodents
Spleen
Spleen - drug effects
Spleen - immunology
Streptozocin
T cell receptors
T helper 17
T regulatory cells
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
type 1 diabetes
title Protective effects of carbonyl iron against multiple low‐dose streptozotocin‐induced diabetes in rodents
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