Anvari E, Fred RG, Welsh N
Pancreas 43 (4) 624-629 [2014-05-00; online 2014-04-11]
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 β-cell destruction. Therefore, the overall aim of this study was to determine whether H(1)-receptor antagonists affect cytokine-induced β-cell death and signaling in vitro. The insulin-producing cell line β-TC6 was exposed to the proinflammatory cytokines interleukin 1β(+) interferon γ, 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 β-catenin levels were analyzed by flow cytometry, real-time polymerase chain reaction, and immunoblotting. 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. Our results indicate a protective effect of a specific H(1)-receptor antagonist.