The H1-receptor antagonist cetirizine protects partially against cytokine- and hydrogen peroxide-induced β-TC6 cell death in vitro.
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 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.


METHODS
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.


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 H(1)-receptor antagonist.
From the Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Ebrahim
E
Anvari
Rikard G
RG
Fred
Nils
N
Welsh
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017332:Cetirizine / Q000494:pharmacology*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000633:toxicity*; D053583:Interleukin-1beta / Q000633:toxicity*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D039563:Histamine H1 Antagonists, Non-Sedating; D053583:Interleukin-1beta; D008263:Macrophage Migration-Inhibitory Factors; D016755:Proto-Oncogene Proteins c-jun; D051176:beta Catenin; D009569:Nitric Oxide; D007371:Interferon-gamma; D048031:JNK Mitogen-Activated Protein Kinases; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse; D017332:Cetirizine