Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis

Zoltán H. Németh, Edwin A. Deitch, Csaba Szabo, Jon G. Mabley, Pál Pacher, Zoltán Fekete, Carl J. Hauser, György Haskó

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Na+/H+ exchangers (NHEs) are integral transmembrane proteins found in all mammalian cells. There is substantial evidence indicating that NHEs regulate inflammatory processes. Because intestinal epithelial cells express a variety of NHEs, we tested the possibility that NHEs are also involved in regulation of the epithelial cell inflammatory response. In addition, since the epithelial inflammatory response is an important contributor to mucosal inflammation in inflammatory bowel disease (IBD), we examined the role of NHEs in the modulation of disease activity in a mouse model of IBD. In human gut epithelial cells, NHE inhibition using a variety of agents, including amiloride, 5-(N-methyl-N-isobutyl)amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, harmaline, clonidine, and cimetidine, suppressed interleukin-8 (IL-8) production. The inhibitory effect of NHE inhibition on IL-8 was associated with a decrease in IL-8 mRNA accumulation. NHE inhibition suppressed both activation of the p42/p44 mitogen-activated protein kinase and nuclear factor-κB. Finally, NHE inhibition ameliorated the course of IBD in dextran sulfate-treated mice. Our data demonstrate that inhibition of NHEs may be an approach worthy of pursuing for the treatment of IBD.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume283
Issue number1 46-1
StatePublished - 2002
Externally publishedYes

Fingerprint

Sodium-Hydrogen Antiporter
Enterocytes
Colitis
Inflammatory Bowel Diseases
Interleukin-8
Epithelial Cells
Harmaline
Dextran Sulfate
Amiloride
Mitogen-Activated Protein Kinase 1
Cimetidine
Clonidine
Inflammation
Messenger RNA

Keywords

  • Crohn's disease
  • Cytokines
  • Lipopolysaccharide
  • Mitogen-activated protein kinase
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis. / Németh, Zoltán H.; Deitch, Edwin A.; Szabo, Csaba; Mabley, Jon G.; Pacher, Pál; Fekete, Zoltán; Hauser, Carl J.; Haskó, György.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 283, No. 1 46-1, 2002.

Research output: Contribution to journalArticle

Németh, Zoltán H. ; Deitch, Edwin A. ; Szabo, Csaba ; Mabley, Jon G. ; Pacher, Pál ; Fekete, Zoltán ; Hauser, Carl J. ; Haskó, György. / Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2002 ; Vol. 283, No. 1 46-1.
@article{32ca26e67048458b80ca64ad102c0c18,
title = "Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis",
abstract = "Na+/H+ exchangers (NHEs) are integral transmembrane proteins found in all mammalian cells. There is substantial evidence indicating that NHEs regulate inflammatory processes. Because intestinal epithelial cells express a variety of NHEs, we tested the possibility that NHEs are also involved in regulation of the epithelial cell inflammatory response. In addition, since the epithelial inflammatory response is an important contributor to mucosal inflammation in inflammatory bowel disease (IBD), we examined the role of NHEs in the modulation of disease activity in a mouse model of IBD. In human gut epithelial cells, NHE inhibition using a variety of agents, including amiloride, 5-(N-methyl-N-isobutyl)amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, harmaline, clonidine, and cimetidine, suppressed interleukin-8 (IL-8) production. The inhibitory effect of NHE inhibition on IL-8 was associated with a decrease in IL-8 mRNA accumulation. NHE inhibition suppressed both activation of the p42/p44 mitogen-activated protein kinase and nuclear factor-κB. Finally, NHE inhibition ameliorated the course of IBD in dextran sulfate-treated mice. Our data demonstrate that inhibition of NHEs may be an approach worthy of pursuing for the treatment of IBD.",
keywords = "Crohn's disease, Cytokines, Lipopolysaccharide, Mitogen-activated protein kinase, Ulcerative colitis",
author = "N{\'e}meth, {Zolt{\'a}n H.} and Deitch, {Edwin A.} and Csaba Szabo and Mabley, {Jon G.} and P{\'a}l Pacher and Zolt{\'a}n Fekete and Hauser, {Carl J.} and Gy{\"o}rgy Hask{\'o}",
year = "2002",
language = "English (US)",
volume = "283",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "1 46-1",

}

TY - JOUR

T1 - Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis

AU - Németh, Zoltán H.

AU - Deitch, Edwin A.

AU - Szabo, Csaba

AU - Mabley, Jon G.

AU - Pacher, Pál

AU - Fekete, Zoltán

AU - Hauser, Carl J.

AU - Haskó, György

PY - 2002

Y1 - 2002

N2 - Na+/H+ exchangers (NHEs) are integral transmembrane proteins found in all mammalian cells. There is substantial evidence indicating that NHEs regulate inflammatory processes. Because intestinal epithelial cells express a variety of NHEs, we tested the possibility that NHEs are also involved in regulation of the epithelial cell inflammatory response. In addition, since the epithelial inflammatory response is an important contributor to mucosal inflammation in inflammatory bowel disease (IBD), we examined the role of NHEs in the modulation of disease activity in a mouse model of IBD. In human gut epithelial cells, NHE inhibition using a variety of agents, including amiloride, 5-(N-methyl-N-isobutyl)amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, harmaline, clonidine, and cimetidine, suppressed interleukin-8 (IL-8) production. The inhibitory effect of NHE inhibition on IL-8 was associated with a decrease in IL-8 mRNA accumulation. NHE inhibition suppressed both activation of the p42/p44 mitogen-activated protein kinase and nuclear factor-κB. Finally, NHE inhibition ameliorated the course of IBD in dextran sulfate-treated mice. Our data demonstrate that inhibition of NHEs may be an approach worthy of pursuing for the treatment of IBD.

AB - Na+/H+ exchangers (NHEs) are integral transmembrane proteins found in all mammalian cells. There is substantial evidence indicating that NHEs regulate inflammatory processes. Because intestinal epithelial cells express a variety of NHEs, we tested the possibility that NHEs are also involved in regulation of the epithelial cell inflammatory response. In addition, since the epithelial inflammatory response is an important contributor to mucosal inflammation in inflammatory bowel disease (IBD), we examined the role of NHEs in the modulation of disease activity in a mouse model of IBD. In human gut epithelial cells, NHE inhibition using a variety of agents, including amiloride, 5-(N-methyl-N-isobutyl)amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, harmaline, clonidine, and cimetidine, suppressed interleukin-8 (IL-8) production. The inhibitory effect of NHE inhibition on IL-8 was associated with a decrease in IL-8 mRNA accumulation. NHE inhibition suppressed both activation of the p42/p44 mitogen-activated protein kinase and nuclear factor-κB. Finally, NHE inhibition ameliorated the course of IBD in dextran sulfate-treated mice. Our data demonstrate that inhibition of NHEs may be an approach worthy of pursuing for the treatment of IBD.

KW - Crohn's disease

KW - Cytokines

KW - Lipopolysaccharide

KW - Mitogen-activated protein kinase

KW - Ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=0036084319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036084319&partnerID=8YFLogxK

M3 - Article

VL - 283

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 1 46-1

ER -