In vitro dissection of anti-diabetic effects of compound a, a dissociating glucocorticoid receptor ligand
2015
Authors:
Vujičić, MilicaSaksida, Tamara
Nikolić, Ivana
Stojanović, Ivana D.
Stošić-Grujičić, Stanislava
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Compound A (CpdA), or
2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethyl-ammonium chloride, is a
stable analog of the hydroxyl phenyl aziridine precursor found in the
Namibian shrub Salsola tuberculatiformis Botschantzev. It belongs to the
group of so-called ``dissociated{''} GC receptor ligands that
downmodulate pro-inflammatory gene expression via the transrepression
mechanism, but without physically binding to DNA. We have recently
reported that the in vivo administration of CpdA exerts a strong
protective effect in a pharmacological model of type 1 diabetes in mice.
The goal of this study was to investigate in more detail the effects of
CpdA on multiple immune system components, as well as on target
pancreatic beta cells in direct in vitro exposure. The utility of CpdA
in diabetes prevention was evaluated through its addition to
mitogen-activated spleen, lymph node and peritoneal cells of C57BL/6
mice, and to murine pancreatic islets and INS-1 and RINm5F beta cell
lines. CpdA modulated immune cell-derived cytokine production in vitro
by restraining the pro-inflammatory M1/Th1/Th17 response and switching
it towards an anti-inflammatory Th2 profile. However, it did not
preserve beta cells from the cytotoxic action of inflammatory cytokines.
Thus, the anti-diabetic properties of CpdA are mediated through the
modulation of immune cell differentiation pathways rather than through
rescue of target cells from autoimmune attack.
Keywords:
Compound A; inflammation; macrophage; lymphocyte; beta cellSource:
Archives of Biological Sciences, 2015, 67, 3, 941-947
DOI: 10.2298/ABS141107056V
ISSN: 1821-4339