TY - JOUR
T1 - RX871024 reduces NO production but does not protect against pancreatic beta-cell death induced by proinflammatory cytokines.
AU - Zaitseva, Irina I
AU - Sharoyko, Vladimir
AU - Størling, Joachim
AU - Efendic, Suad
AU - Guerin, Christopher
AU - Mandrup-Poulsen, Thomas
AU - Nicotera, Pierluigi
AU - Berggren, Per-Olof
AU - Zaitsev, Sergei V
N1 - Keywords: Animals; Benzofurans; Cell Death; Cells, Cultured; Cytokines; Imidazoles; Indoles; Insulin; Insulin-Secreting Cells; Interferon Type II; Interleukin-1; Mice; Mice, Obese; Nitric Oxide; Tumor Necrosis Factor-alpha
PY - 2006
Y1 - 2006
N2 - The imidazoline compound RX871024 reduces IL-1beta-induced NO production thereby protecting against IL-1beta-induced beta-cell apoptosis. The aim of this study was to evaluate whether imidazolines RX871024 and efaroxan protect beta-cells against death in the presence of a combination of the cytokines IL-1beta, IFNgamma, and TNFalpha. To address this issue, experiments involving different methods for detection of cell death, different concentrations of the cytokines, and a variety of conditions of preparation and culturing of ob/ob mouse islets and beta-cells have been carried out. Thoroughly performed experiments have not been able to demonstrate a protective effect of RX871024 and efaroxan on beta-cell death induced by the combination of cytokines. However, the inhibitory effect of RX871024 on NO production in ob/ob mouse islets and beta-cells was still observed in the presence of all three cytokines and correlated with the decrease in p38 MAPK phosphorylation. Conversely, efaroxan did not affect cytokine-induced NO production. Our data indicate that a combination of pro-inflammatory cytokines IL-1beta, IFNgamma, and TNFalpha, conditions modelling those that take place in type 1 diabetes, induces pancreatic beta-cell death that does not directly correlate with NO production and cannot be counteracted with imidazoline compounds.
AB - The imidazoline compound RX871024 reduces IL-1beta-induced NO production thereby protecting against IL-1beta-induced beta-cell apoptosis. The aim of this study was to evaluate whether imidazolines RX871024 and efaroxan protect beta-cells against death in the presence of a combination of the cytokines IL-1beta, IFNgamma, and TNFalpha. To address this issue, experiments involving different methods for detection of cell death, different concentrations of the cytokines, and a variety of conditions of preparation and culturing of ob/ob mouse islets and beta-cells have been carried out. Thoroughly performed experiments have not been able to demonstrate a protective effect of RX871024 and efaroxan on beta-cell death induced by the combination of cytokines. However, the inhibitory effect of RX871024 on NO production in ob/ob mouse islets and beta-cells was still observed in the presence of all three cytokines and correlated with the decrease in p38 MAPK phosphorylation. Conversely, efaroxan did not affect cytokine-induced NO production. Our data indicate that a combination of pro-inflammatory cytokines IL-1beta, IFNgamma, and TNFalpha, conditions modelling those that take place in type 1 diabetes, induces pancreatic beta-cell death that does not directly correlate with NO production and cannot be counteracted with imidazoline compounds.
U2 - 10.1016/j.bbrc.2006.06.197
DO - 10.1016/j.bbrc.2006.06.197
M3 - Journal article
C2 - 16870144
SN - 0006-291X
VL - 347
SP - 1121
EP - 1128
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
