Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice
- Author
- T Saksida, M Vujicic, I Nikolic, I Stojanovic, Guy Haegeman (UGent) and S Stosic-Grujicic
- Organization
- Abstract
- Background and Purpose: Type 1 diabetes is a multifactorial inflammatory disease that develops as a result of deregulated immune responses, causing progressive autoimmune destruction of insulin-producing beta cells of pancreas. 2-((4-acetoxyphenyl)-2-chloro-N-methyl) ethylammonium chloride, compound A (CpdA), is a selective glucocorticoid receptor (GR) agonist that displays strong anti-inflammatory and immunomodulatory activities. We investigated the therapeutic effectiveness of CpdA in a pharmacological model of type 1 diabetes in mice. Experimental Approach: The utility of CpdA in diabetes prevention was evaluated in vivo through its prophylactic administration to male C57BL/6 mice that received multiple low doses of streptozotocin for immunoinflammatory diabetes induction. The effect of CpdA on disease development was studied by measuring blood glucose and insulin level, histopathological examination, determination of the nature of infiltrating cells, pro- and anti-inflammatory cytokine production, and signalling pathways. Key Results: Prophylactic in vivo therapy with CpdA conferred protection against development of immunoinflammatory diabetes in mice by dampening the M1/Th1/Th17 immune response and switching it towards an anti-inflammatory M2/Th2/Treg profile, thus preserving beta cell function. Conclusions and Implications: Anti-diabetic properties of CpdA are mediated through modulation of immune cell-mediated pathways, but without triggering adverse events. These findings provide basic information for the therapeutic use of selective GR agonists in the amelioration of islet-directed autoimmunity.
- Keywords
- COLLAGEN-INDUCED ARTHRITIS, NF-KAPPA-B, IN-VIVO, REGULATORY T-CELLS, ISLET-DIRECTED AUTOIMMUNITY, MOUSE MODEL, PLANT-ORIGIN, ARRIVE GUIDELINES, INFLAMMATION, M2 MACROPHAGES
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-5840140
- MLA
- Saksida, T., et al. “Compound A, a Selective Glucocorticoid Receptor Agonist, Inhibits Immunoinflammatory Diabetes, Induced by Multiple Low Doses of Streptozotocin in Mice.” BRITISH JOURNAL OF PHARMACOLOGY, vol. 171, no. 24, 2014, pp. 5898–909, doi:10.1111/bph.12892.
- APA
- Saksida, T., Vujicic, M., Nikolic, I., Stojanovic, I., Haegeman, G., & Stosic-Grujicic, S. (2014). Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice. BRITISH JOURNAL OF PHARMACOLOGY, 171(24), 5898–5909. https://doi.org/10.1111/bph.12892
- Chicago author-date
- Saksida, T, M Vujicic, I Nikolic, I Stojanovic, Guy Haegeman, and S Stosic-Grujicic. 2014. “Compound A, a Selective Glucocorticoid Receptor Agonist, Inhibits Immunoinflammatory Diabetes, Induced by Multiple Low Doses of Streptozotocin in Mice.” BRITISH JOURNAL OF PHARMACOLOGY 171 (24): 5898–5909. https://doi.org/10.1111/bph.12892.
- Chicago author-date (all authors)
- Saksida, T, M Vujicic, I Nikolic, I Stojanovic, Guy Haegeman, and S Stosic-Grujicic. 2014. “Compound A, a Selective Glucocorticoid Receptor Agonist, Inhibits Immunoinflammatory Diabetes, Induced by Multiple Low Doses of Streptozotocin in Mice.” BRITISH JOURNAL OF PHARMACOLOGY 171 (24): 5898–5909. doi:10.1111/bph.12892.
- Vancouver
- 1.Saksida T, Vujicic M, Nikolic I, Stojanovic I, Haegeman G, Stosic-Grujicic S. Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice. BRITISH JOURNAL OF PHARMACOLOGY. 2014;171(24):5898–909.
- IEEE
- [1]T. Saksida, M. Vujicic, I. Nikolic, I. Stojanovic, G. Haegeman, and S. Stosic-Grujicic, “Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice,” BRITISH JOURNAL OF PHARMACOLOGY, vol. 171, no. 24, pp. 5898–5909, 2014.
@article{5840140, abstract = {{Background and Purpose: Type 1 diabetes is a multifactorial inflammatory disease that develops as a result of deregulated immune responses, causing progressive autoimmune destruction of insulin-producing beta cells of pancreas. 2-((4-acetoxyphenyl)-2-chloro-N-methyl) ethylammonium chloride, compound A (CpdA), is a selective glucocorticoid receptor (GR) agonist that displays strong anti-inflammatory and immunomodulatory activities. We investigated the therapeutic effectiveness of CpdA in a pharmacological model of type 1 diabetes in mice. Experimental Approach: The utility of CpdA in diabetes prevention was evaluated in vivo through its prophylactic administration to male C57BL/6 mice that received multiple low doses of streptozotocin for immunoinflammatory diabetes induction. The effect of CpdA on disease development was studied by measuring blood glucose and insulin level, histopathological examination, determination of the nature of infiltrating cells, pro- and anti-inflammatory cytokine production, and signalling pathways. Key Results: Prophylactic in vivo therapy with CpdA conferred protection against development of immunoinflammatory diabetes in mice by dampening the M1/Th1/Th17 immune response and switching it towards an anti-inflammatory M2/Th2/Treg profile, thus preserving beta cell function. Conclusions and Implications: Anti-diabetic properties of CpdA are mediated through modulation of immune cell-mediated pathways, but without triggering adverse events. These findings provide basic information for the therapeutic use of selective GR agonists in the amelioration of islet-directed autoimmunity.}}, author = {{Saksida, T and Vujicic, M and Nikolic, I and Stojanovic, I and Haegeman, Guy and Stosic-Grujicic, S}}, issn = {{0007-1188}}, journal = {{BRITISH JOURNAL OF PHARMACOLOGY}}, keywords = {{COLLAGEN-INDUCED ARTHRITIS,NF-KAPPA-B,IN-VIVO,REGULATORY T-CELLS,ISLET-DIRECTED AUTOIMMUNITY,MOUSE MODEL,PLANT-ORIGIN,ARRIVE GUIDELINES,INFLAMMATION,M2 MACROPHAGES}}, language = {{eng}}, number = {{24}}, pages = {{5898--5909}}, title = {{Compound A, a selective glucocorticoid receptor agonist, inhibits immunoinflammatory diabetes, induced by multiple low doses of streptozotocin in mice}}, url = {{http://doi.org/10.1111/bph.12892}}, volume = {{171}}, year = {{2014}}, }
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