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J. Biol. Chem., Vol. 277, Issue 10, 7713-7719, March 8, 2002
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From the Department of Surgery, UMD-New Jersey Medical School,
Newark, New Jersey 07103
Lithium has been documented to regulate
apoptosis and apoptotic gene expression via NF-
Lithium Induces NF-
B Activation and Interleukin-8 Production
in Human Intestinal Epithelial Cells*
B and
mitogen-activated protein (MAP) kinase-dependent
mechanisms. Since both NF-B and MAP kinases are also important
mediators of inflammatory gene expression, we investigated the effect
of lithium on NF-B- and MAP kinase-mediated inflammatory gene
expression. Incubation of human intestinal epithelial cells with
lithium induced both enhanced NF-B DNA binding and NF-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-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-B and MAP kinase activation.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Surgery,
UMD-New Jersey Medical School, 185 S. Orange Ave., University Heights,
Newark, NJ 07103. Tel.: 973-972-8694; Fax: 973-972-6803; E-mail:
haskoge@umdnj.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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