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The H-1-Receptor Antagonist Cetirizine Protects Partially Against Cytokine- and Hydrogen Peroxide-Induced beta-TC6 Cell Death In Vitro
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2014 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, no 4, 624-629 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
JNK, nitric oxide, beta-catenin, beta-cell destruction, H1-receptor antagonists
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:uu:diva-225010DOI: 10.1097/MPA.0000000000000076ISI: 000334787400020OAI: oai:DiVA.org:uu-225010DiVA: diva2:719636
Available from: 2014-05-26 Created: 2014-05-26 Last updated: 2017-12-05Bibliographically approved

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Anvari, EbrahimFred, Rikard G.Welsh, Nils

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