Lithium induces NF-κB activation and interleukin-8 production in human intestinal epithelial cells

Zoltán H. Németh, Edwin A. Deitch, Csaba Szabó, Zoltán Fekete, Carl J. Hauser, György Haskó

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    53 Scopus citations

    Abstract

    Lithium has been documented to regulate apoptosis and apoptotic gene expression via NF-κB and mitogen-activated protein (MAP) kinase-dependent mechanisms. Since both NF-κB and MAP kinases are also important mediators of inflammatory gene expression, we investigated the effect of lithium on NF-κB- and MAP kinase-mediated inflammatory gene expression. Incubation of human intestinal epithelial cells with lithium induced both enhanced NF-κB DNA binding and NF-κB-dependent transcriptional activity. In addition, lithium stimulated activation of both the p38 and p42/44 MAP kinases. This lithium-induced up-regulation of NF-κB and MAP kinase activation was associated with an enhancement of interleukin-8 mRNA accumulation as well as an increase in interleukin-8 protein release. These proinflammatory effects of lithium were, in large part, mediated by activation of Na+/H+ exchangers, because selective blockade of Na+/H+ exchangers prevented the lithium-induced intestinal cell inflammatory response. These results demonstrate that lithium stimulates inflammatory gene expression via NF-κB and MAP kinase activation.

    Original languageEnglish (US)
    Pages (from-to)7713-7719
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume277
    Issue number10
    DOIs
    StatePublished - Mar 8 2002

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    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Németh, Z. H., Deitch, E. A., Szabó, C., Fekete, Z., Hauser, C. J., & Haskó, G. (2002). Lithium induces NF-κB activation and interleukin-8 production in human intestinal epithelial cells. Journal of Biological Chemistry, 277(10), 7713-7719. https://doi.org/10.1074/jbc.M109711200