Insulin like growth factor-1 activates nuclear factor-kappa B and increases transcription of the intercellular adhesion molecule-1 gene in endothelial cells
Sk. Balaram et al., Insulin like growth factor-1 activates nuclear factor-kappa B and increases transcription of the intercellular adhesion molecule-1 gene in endothelial cells, CARDIOV SUR, 7(1), 1999, pp. 91-97
A critical early event in the pathogenesis of occlusive vascular disease is
the adhesion of monocytes to endothelial cells, The authors have previousl
y reported that insulin-like growth factor-1 increases monocyte-endothelial
cell adhesion and increases the expression of intercellular adhesion molec
ule-1. In this study, it is hypothesized that the upregulation of intercell
ular adhesion molecule-1 expression after treatment with insulin-like growt
h factor-1 is caused by an increase in the transcription of intercellular a
dhesion molecule-1 in endothelial cells, and that this transcription is reg
ulated, at least in part, by activation of nuclear factor-kappa B, Adherenc
e cell assays were performed using insulin-like growth factor-1 treated hum
an umbilical vein endothelial cells and human monocytes, To determine the r
ole of nuclear factor-kappa B, Western blotting using the anti-p65 (activat
ed portion of nuclear factor-kappa B) was performed on cell lysate of human
umbilical vein endothelial cells treated with insulin-like growth factor-1
. RT-PCR was performed on RNA extracted from insulin-like growth factor-1-t
reated human umbilical vein endothelial cells, Intercellular adhesion molec
ule-1 antibody attenuated the increase in monocyte-endothelial cell adhesio
n of endothelial cells exposed to insulin-like growth factor-1, We observed
an increase in expression of the activated nuclear factor-kappa B p65 prot
ein in response to insulin-like growth factor-1 treatment. Peak increase oc
curred at 30 min. This effect was sensitive to pretreatment of human umbili
cal vein endothelial cells with the insulinlike growth factor-1 receptor an
tibody, Human umbilical vein endothelial cells treated with insulin-like gr
owth factor-1 for 2 and 4 h revealed a significant increase in intercellula
r adhesion molecule-1 mRNA as compared with untreated human umbilical vein
endothelial cells. Tumor necrosis factor-alpha produced a larger increase i
n intercellular adhesion molecule-1 mRNA expression. These results suggest
that insulin-like growth factor-1 enhances intercellular adhesion molecule-
1 transcription and activates nuclear factor-kappa B in endothelial cells.
The intracellular pathways that increase cell adhesion molecule expression
may provide a common link to understanding the monocyte-endothelial cell ad
hesion that occurs in the early stages of atherosclerosis and restenosis. (
C) 1998 The International Society for Cardiovascular Surgery. Published by
Elsevier Science Ltd. All rights reserved.