Inhibition of the Na+/H+ antiporter suppresses IL-12 p40 production by mouse macrophages
Nemeth, Z.H., Mabley, J.G., Deitch, E.A., Szabo, C. and Hasko, G. (2001) Inhibition of the Na+/H+ antiporter suppresses IL-12 p40 production by mouse macrophages Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1539 (3). pp. 233-242. ISSN 0167-4889
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Official URL: http://dx.doi.org/10.1016/S0167-4889(01)00111-2
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.
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