Glabridin Suppresses Intercellular Adhesion Molecule-1 Expression in Tumor Necrosis Factor-α-Stimulated Human Umbilical Vein Endothelial Cells by Blocking Sphingosine Kinase Pathway: Implications of Akt, Extracellular Signal-Regulated Kinase, and Nuclear Factor-κB/Rel Signaling Pathways

2005 ◽  
Vol 69 (3) ◽  
pp. 941-949 ◽  
Author(s):  
Jong Soon Kang ◽  
Yeo Dae Yoon ◽  
Mi Hwa Han ◽  
Sang-Bae Han ◽  
Kiho Lee ◽  
...  
2000 ◽  
Vol 278 (3) ◽  
pp. H853-H861 ◽  
Author(s):  
Cameron W. Lush ◽  
Gediminas Cepinskas ◽  
Peter R. Kvietys

Cytokine release from inflammatory (CD14+) cells is reduced after repeated stimulation with lipopolysaccharide (LPS; LPS tolerance). However, it is not known whether LPS tolerance can be induced in CD14−cells. The aim of the present study was to determine whether endothelial cells [human umbilical vein endothelial cells (HUVEC)] could be rendered tolerant to LPS with respect to LPS-induced polymorphonuclear neutrophil (PMN) adhesion. LPS stimulation (0.5 μg/ml; 4 h) of naive HUVEC increased PMN adhesion. Pretreatment of HUVEC with LPS (0.5 μg/ml) for 24 h resulted in a reduction in the proadhesive effects of a subsequent LPS challenge. The initial LPS stimulation increased 1) mobilization of the nuclear transcription factor NF-κB to the nucleus and 2) surface levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and E-selectin. In LPS-tolerant HUVEC, a second LPS challenge resulted in 1) less accumulation of NF-κB in the nucleus, 2) a reduction in E-selectin expression, and 3) unchanged ICAM-1 expression. LPS-tolerant cells were still capable of mobilizing NF-κB in response to stimulation with either interleukin-1β or tumor necrosis factor-α, resulting in elevated E-selectin levels and increased PMN adhesion. These studies show for the first time that LPS tolerance can be induced in endothelial cells with respect to PMN adhesion. This tolerance is specific for LPS and is associated with an inability of LPS to mobilize NF-κB, resulting in less E-selectin expression.


Sign in / Sign up

Export Citation Format

Share Document