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

Z.H. Nemeth, Jon Mabley, E.A. Deitch, C. Szabo, G. Hasko

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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
Pages (from-to)233-242
Number of pages10
JournalBiochimica et Biophysica Acta (BBA) - Molecular Cell Research
Issue number3
Publication statusPublished - Jun 2001


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


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