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

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

Research output: Contribution to journalArticle

53 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Interleukin-8
Lithium
Mitogen-Activated Protein Kinases
Epithelial Cells
Chemical activation
Gene expression
Gene Expression
Sodium-Hydrogen Antiporter
Mitogen-Activated Protein Kinase 1
Up-Regulation
Apoptosis
Messenger RNA
DNA
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lithium induces NF-κB activation and interleukin-8 production in human intestinal epithelial cells. / Németh, Zoltán H.; Deitch, Edwin A.; Szabo, Csaba; Fekete, Zoltán; Hauser, Carl J.; Haskó, György.

In: Journal of Biological Chemistry, Vol. 277, No. 10, 08.03.2002, p. 7713-7719.

Research output: Contribution to journalArticle

Németh, Zoltán H. ; Deitch, Edwin A. ; Szabo, Csaba ; Fekete, Zoltán ; Hauser, Carl J. ; Haskó, György. / Lithium induces NF-κB activation and interleukin-8 production in human intestinal epithelial cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 10. pp. 7713-7719.
@article{7e180aaf5a524788882c678432e6a674,
title = "Lithium induces NF-κB activation and interleukin-8 production in human intestinal epithelial cells",
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.",
author = "N{\'e}meth, {Zolt{\'a}n H.} and Deitch, {Edwin A.} and Csaba Szabo and Zolt{\'a}n Fekete and Hauser, {Carl J.} and Gy{\"o}rgy Hask{\'o}",
year = "2002",
month = "3",
day = "8",
doi = "10.1074/jbc.M109711200",
language = "English (US)",
volume = "277",
pages = "7713--7719",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",

}

TY - JOUR

T1 - Lithium induces NF-κB activation and interleukin-8 production in human intestinal epithelial cells

AU - Németh, Zoltán H.

AU - Deitch, Edwin A.

AU - Szabo, Csaba

AU - Fekete, Zoltán

AU - Hauser, Carl J.

AU - Haskó, György

PY - 2002/3/8

Y1 - 2002/3/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037040903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037040903&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109711200

DO - 10.1074/jbc.M109711200

M3 - Article

VL - 277

SP - 7713

EP - 7719

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 10

ER -