RX871024 reduces NO production but does not protect against pancreatic beta-cell death induced by proinflammatory cytokines.
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Biochemical and Biophysical Research Communications |
Volume | 347 |
Issue number | 4 |
Pages (from-to) | 1121-8 |
Number of pages | 7 |
ISSN | 0006-291X |
DOIs | |
Publication status | Published - 2006 |
Bibliographical note
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
ID: 8465677