RX871024 reduces NO production but does not protect against pancreatic β-cell death induced by proinflammatory cytokines. / Zaitseva, Irina I.; Sharoyko, Vladimir; Størling, Joachim; Efendic, Suad; Guerin, Christopher; Mandrup-Poulsen, Thomas; Nicotera, Pierluigi; Berggren, Per Olof; Zaitsev, Sergei V.
In: Biochemical and Biophysical Research Communications, Vol. 347, No. 4, 08.09.2006, p. 1121-1128.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - RX871024 reduces NO production but does not protect against pancreatic β-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.
PY - 2006/9/8
Y1 - 2006/9/8
N2 - The imidazoline compound RX871024 reduces IL-1β-induced NO production thereby protecting against IL-1β-induced β-cell apoptosis. The aim of this study was to evaluate whether imidazolines RX871024 and efaroxan protect β-cells against death in the presence of a combination of the cytokines IL-1β, IFNγ, and TNFα. 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 β-cells have been carried out. Thoroughly performed experiments have not been able to demonstrate a protective effect of RX871024 and efaroxan on β-cell death induced by the combination of cytokines. However, the inhibitory effect of RX871024 on NO production in ob/ob mouse islets and β-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-1β, IFNγ, and TNFα, conditions modelling those that take place in type 1 diabetes, induces pancreatic β-cell death that does not directly correlate with NO production and cannot be counteracted with imidazoline compounds.
AB - The imidazoline compound RX871024 reduces IL-1β-induced NO production thereby protecting against IL-1β-induced β-cell apoptosis. The aim of this study was to evaluate whether imidazolines RX871024 and efaroxan protect β-cells against death in the presence of a combination of the cytokines IL-1β, IFNγ, and TNFα. 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 β-cells have been carried out. Thoroughly performed experiments have not been able to demonstrate a protective effect of RX871024 and efaroxan on β-cell death induced by the combination of cytokines. However, the inhibitory effect of RX871024 on NO production in ob/ob mouse islets and β-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-1β, IFNγ, and TNFα, conditions modelling those that take place in type 1 diabetes, induces pancreatic β-cell death that does not directly correlate with NO production and cannot be counteracted with imidazoline compounds.
KW - Apoptosis
KW - Cytokine
KW - Imidazoline
KW - Insulin
KW - Islet of langerhans
KW - MAPK
KW - TUNEL labelling
UR - http://www.scopus.com/inward/record.url?scp=33746343031&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.06.197
DO - 10.1016/j.bbrc.2006.06.197
M3 - Article
C2 - 16870144
VL - 347
SP - 1121
EP - 1128
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -
ID: 5533136