Details

Autor(en) / Beteiligte

• Todaro, Matilde
• Di Gaudio, Francesca
• Lavitrano, Marialuisa
• Stassi, Giorgio
• Papaccio, Gianpaolo

Titel

Islet beta-cell apoptosis triggered in vivo by interleukin-1beta is not related to the inducible nitric oxide synthase pathway: evidence for mitochondrial function impairment and lipoperoxidation

Ist Teil von

• Endocrinology (Philadelphia), 2003-10, Vol.144 (10), p.4264-4271

Ort / Verlag

United States

Erscheinungsjahr

2003

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• IL-1beta is recognized as an effector cytokine contributing to islet beta-cell destruction during diabetes. We have previously shown in vitro that IL-1beta induces nitric oxide (NO) and beta-cell damage. Here, we show that IL-1beta administration in vivo to Wistar rats transiently increases manganese superoxide dismutase activity, whereas inducible NO synthase is not detected, and the levels of nitrate+nitrate do not change. Moreover, a significant decrease of mitochondrial aconitase, leading to a rise of hydroperoxides, and islet beta-cell apoptosis, involving caspase-3 and -8, is observed. Analysis of adhesion molecules in beta-cells showed that intercellular adhesion molecule-1 is highly expressed 48 h after IL-1beta administration and that this is concomitant to the fall of manganese superoxide dismutase activity. Thus, IL-1beta exerts a proapoptotic effect in vivo through mitochondrial enzyme alteration, which is not related to the inducible NO synthase pathway, and dysregulates the immune system through the up-regulation of adhesion molecules.