Divergent effect of mometasone on human eosinophil and neutrophil apoptosis

Xianzhi Zhang, Eeva Moilanen, Ian M. Adcock, Mark A. Lindsay, Hannu Kankaanranta

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Mometasone is a potent synthetic glucocorticoid, which is under development as an inhaled preparation for the treatment of asthma. Previous studies have suggested that glucocorticoids have direct effects on human eosinophil and neutrophil apoptosis. The present study was designed to characterize the effects of mometasone on constitutive apoptosis and cytokine-afforded survival in isolated human eosinophils and neutrophils. The isolated eosinophils or neutrophils were cultured in vitro, and apoptosis was assessed by flow cytometric analysis of relative DNA content, by annexin-V binding and morphological analysis. Mometasone enhanced constitutive human eosinophil apoptosis in a concentration-dependent manner. The maximal enhancement of eosinophil apoptosis was 2.1-fold with an EC50 value of 5.63 ± 2.33 nM. This enhancing effect was reversed by the glucocorticoid receptor antagonist, mifepristone. In the presence of added cytokines, mometasone reversed tumor necrosis factor -α-induced eosinophil survival but not that afforded by interleukin -5. In contrast, mometasone inhibited human neutrophil apoptosis in a concentration-dependent manner. The maximal inhibition of neutrophil apoptosis was 50% with an EC50 value of 0.17 ± 0.03 nM. The inhibitory effect was partly reversed by mifepristone. In the presence of added cytokines, mometasone further enhanced neutrophil survival induced by the granulocyte-macrophage colony-stimulating factor and leukotriene B4. The present data suggests that mometasone has opposite effects on apoptosis of human eosinophils and neutrophils at clinically relevant drug concentrations via an effect on glucocorticoid receptor. © 2002 Elsevier Science Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)1523-1534
    Number of pages11
    JournalLife Sciences
    Volume71
    Issue number13
    DOIs
    Publication statusPublished - 16 Aug 2002

    Keywords

    • Apoptosis
    • Eosinophil
    • Mometasone furoate
    • Neutrophil

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