H. Glazebrook et al., REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I EXPRESSION IN VASCULAR ENDOTHELIAL-CELLS BY THE INFLAMMATORY CYTOKINE INTERLEUKIN-1, Journal of vascular research, 35(3), 1998, pp. 143-149
Insulin-like growth factor-1 (IGF-1) has important roles in vascular p
hysiology and pathologies such as atherosclerosis, However, the factor
s that control expression of this growth factor in human vascular cell
s are largely unknown. In this study the effects of the inflammatory c
ytokine interleukin-1 (IL-1) on IGF-1 mRNA and peptide synthesis was e
xamined in human endothelial cells. Cultured human umbilical vein endo
thelial (HUVE) cells were challenged with interleukin-1 and IGF-1 Ea a
nd Eb mRNA levels were determined by nuclease protection assays and re
verse transcription/polymerase chain reaction. IL-1 caused a dramatic
increase in IGF-1 Ea mRNA in HUVE cells. Transcript levels peaked betw
een 2 and 4 h of IL-1 treatment and declined over the subsequent 4 h,
Consistent with its effect on mRNA, the inflammatory cytokine causes a
3-fold stimulation in production of IGF-1 peptide from endothelial ce
lls. These results demonstrate increased IGF-1 mRNA and peptide in vas
cular endothelial cells stimulated with IL-1. This suggests that under
conditions of local inflammation at the vessel wall the direct action
of IL-1 on endothelium can lead to induction of IGF-1 which could pro
mote the intimal hyperplasia often seen in these circumstances.