Inhibition of the Na+/H+ antiporter suppresses IL-12 p40 production by mouse macrophages

Zoltán H. Németh, John G. Mabley, Edwin A. Deitch, Csaba Szabó, György Haskó

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    26 Scopus citations

    Abstract

    The amiloride-inhibitable Na+/H+ antiporter plays an important role in macrophage activation. The intracellular pathways leading to interleukin (IL)-12 p40 production by activated macrophages are incompletely understood. In the present study, we examined the contribution of the Na+/H+ antiporter to the production of IL-12 p40. Amiloride or its analogs decreased the production of IL-12 p40 in macrophages stimulated with bacterial lipopolysaccharide and interferon-γ. The order of potency of amiloride analogs was consistent with the proposition that the effect of amiloride is mediated by the inhibition of the Na+/H+ antiporter. The effect of amiloride was post-transcriptional, as IL-12 p40 mRNA levels induced by lipopolysaccharide and interferon-γ were not affected by this inhibitor. Furthermore, the inhibitory effect of amiloride on IL-12 p40 production was not a result of interference with the activation of the p38 and p42/44 mitogen-activated protein kinases or c-Jun kinase. In summary, the production of IL-12 p40 requires a functional Na+/H+ antiporter.

    Original languageEnglish (US)
    Pages (from-to)233-242
    Number of pages10
    JournalBiochimica et Biophysica Acta - Molecular Cell Research
    Volume1539
    Issue number3
    DOIs
    StatePublished - Jun 20 2001

    Keywords

    • Autoimmune disease
    • Cytokine
    • Inflammation
    • Monocyte
    • Shock
    • T helper 1/T helper 2

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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