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The H1-Receptor Antagonist Cetirizine Protects Partially Against Cytokine- and Hydrogen Peroxide–Induced β-TC6 Cell Death In Vitro

Anvari, Ebrahim MD; Fred, Rikard G. PhD; Welsh, Nils MD, PhD

doi: 10.1097/MPA.0000000000000076
Original Articles
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Objective It has been proposed that the histamine 1 (H1) 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 H1-receptor antagonist cetirizine can counteract the activation of signals/factors pertinent to the pathogenesis of type 1 diabetes and cytokine-induced β-cell destruction. Therefore, the overall aim of this study was to determine whether H1-receptor antagonists affect cytokine-induced β-cell death and signaling in vitro.

Methods The insulin-producing cell line β-TC6 was exposed to the proinflammatory cytokines interleukin 1β+ interferon γ, or hydrogen peroxide. The H1-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 β-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 β-TC6 cell contents of β-catenin at basal conditions.

Conclusions Our results indicate a protective effect of a specific H1-receptor antagonist.

From the Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.

Received for publication November 30, 2012; accepted December 19, 2013.

Reprints: Nils Welsh, MD, PhD, Department of Medical Cell Biology, Husargatan 3, Box 571 BMC, 75123 Uppsala, Sweden (e-mail: nils.welsh@mcb.uu.se).

This study was supported in part by the Swedish Research Council (2010-11564-15-3), the Swedish Diabetes Association, the family Ernfors Fund, Barndiabetesfonden, and the Novo-Nordisk Foundation.

The authors declare no conflict of interest.

© 2014 by Lippincott Williams & Wilkins.