The H-1-Receptor Antagonist Cetirizine Protects Partially Against Cytokine- and Hydrogen Peroxide-Induced beta-TC6 Cell Death In Vitro
2014 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, no 4, 624-629 p.Article in journal (Refereed) Published
Objective It has been proposed that the histamine 1 (H-1) receptor not only promotes allergic reactions but also modulates autoimmune diseases, such as type 1 diabetes. In line with this, it has recently been reported that the H-1-receptor antagonist cetirizine can counteract the activation of signals/factors pertinent to the pathogenesis of type 1 diabetes and cytokine-induced beta-cell destruction. Therefore, the overall aim of this study was to determine whether H-1-receptor antagonists affect cytokine-induced beta-cell death and signaling in vitro. Methods The insulin-producing cell line beta-TC6 was exposed to the proinflammatory cytokines interleukin 1 beta(+) interferon gamma, or hydrogen peroxide. The H-1-receptor antagonists desloratadine and cetirizine were added to the cell cultures and cell viability; macrophage inhibitory factor levels, c-Jun N-terminal kinase phosphorylation, c-Jun expression, and beta-catenin levels were analyzed by flow cytometry, real-time polymerase chain reaction, and immunoblotting. Results Cetirizine protected partially against both cytokine- and hydrogen peroxide-induced cell death. This effect was paralleled by an inhibition of cytokine-induced c-Jun N-terminal kinase phosphorylation, c-Jun induction, and a restoration of macrophage inhibitory factor contents. Cetirizine also increased the beta-TC6 cell contents of beta-catenin at basal conditions. Conclusions Our results indicate a protective effect of a specific H-1-receptor antagonist.
Place, publisher, year, edition, pages
2014. Vol. 43, no 4, 624-629 p.
JNK, nitric oxide, beta-catenin, beta-cell destruction, H1-receptor antagonists
Gastroenterology and Hepatology
IdentifiersURN: urn:nbn:se:uu:diva-225010DOI: 10.1097/MPA.0000000000000076ISI: 000334787400020OAI: oai:DiVA.org:uu-225010DiVA: diva2:719636