NHE blockade inhibits chemokine production and NF-κB activation in immunostimulated endothelial cells

Zoltán H. Németh, Edwin A. Deitch, Qi Lu, Csaba Szabo, György Haskó

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Na+/H+ exchanger (NHE) activation has been documented to contribute to endothelial cell injury caused by inflammatory states. However, the role of NHEs in regulation of the endothelial cell inflammatory response has not been investigated. The present study tested the hypothesis that NHEs contribute to endothelial cell inflammation induced by endotoxin or interleukin (IL)-1β. NHE inhibition using amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, and 5-(N-methyl-N-isobutyl)amiloride as well as the non-amiloride NHE inhibitors cimetidine, clonidine, and harmaline suppressed endotoxin-induced IL-8 and monocyte chemoattractant protein (MCP)-1 production by human umbilical endothelial vein cells (HUVECs). The suppressive effect of amiloride on endotoxin-induced IL-8 production was associated with a decreased accumulation of IL-8 mRNA. NHE inhibitors suppressed both inhibitory (I)κB degradation and nuclear factor (NF)-κB DNA binding, suggesting that a decrease in activation of the IκB-NF-κB system contributed to the suppression of HUVEC inflammatory response by NHE blockade. NHE inhibition decreased also the IL-1β-induced HUVEC inflammatory response, because amiloride suppressed IL-1β-induced E-selectin expression on HUVECs. These results demonstrate that maximal activation of the HUVEC inflammatory response requires a functional NHE.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number2 52-2
StatePublished - 2002
Externally publishedYes

Fingerprint

Sodium-Hydrogen Antiporter
Endothelial cells
Chemokines
Human Umbilical Vein Endothelial Cells
Endothelial Cells
Chemical activation
Amiloride
Interleukin-8
Interleukin-1
Endotoxins
Harmaline
E-Selectin
Chemokine CCL2
Cimetidine
Clonidine
Corrosion inhibitors
Inflammation
Messenger RNA
DNA
Degradation

Keywords

  • Adhesion molecule
  • Cytokines
  • Inflammation
  • Na/H exchanger
  • Sepsis
  • Transcription factors

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

NHE blockade inhibits chemokine production and NF-κB activation in immunostimulated endothelial cells. / Németh, Zoltán H.; Deitch, Edwin A.; Lu, Qi; Szabo, Csaba; Haskó, György.

In: American Journal of Physiology - Cell Physiology, Vol. 283, No. 2 52-2, 2002.

Research output: Contribution to journalArticle

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AU - Haskó, György

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