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. 2002 Mar 8;277(10):7713-9.
doi: 10.1074/jbc.M109711200. Epub 2001 Dec 27.

Lithium Induces NF-kappa B Activation and interleukin-8 Production in Human Intestinal Epithelial Cells

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Lithium Induces NF-kappa B Activation and interleukin-8 Production in Human Intestinal Epithelial Cells

Zoltán H Németh et al. J Biol Chem. .
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Abstract

Lithium has been documented to regulate apoptosis and apoptotic gene expression via NF-kappa B and mitogen-activated protein (MAP) kinase-dependent mechanisms. Since both NF-kappa B and MAP kinases are also important mediators of inflammatory gene expression, we investigated the effect of lithium on NF-kappa B- and MAP kinase-mediated inflammatory gene expression. Incubation of human intestinal epithelial cells with lithium induced both enhanced NF-kappa B DNA binding and NF-kappa B-dependent transcriptional activity. In addition, lithium stimulated activation of both the p38 and p42/44 MAP kinases. This lithium-induced up-regulation of NF-kappa B 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-kappa B and MAP kinase activation.

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