@article{
author = "Saksida, Tamara and Vujičić, Milica and Nikolić, Ivana and Stojanović, Ivana D. and Haegeman, G. and Stošić-Grujičić, Stanislava",
year = "2014",
abstract = "Background and PurposeType 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 ApproachThe 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 ResultsProphylactic 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 ImplicationsAnti-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.",
journal = "British Journal of Pharmacology",
title = "Compound A, a selective glucocorticoid receptor agonist, inhibits
immunoinflammatory diabetes, induced by multiple low doses of
streptozotocin in mice",
number = "24, SI",
volume = "171",
doi = "10.1111/bph.12892",
pages = "5898-5909"
}