Regulation of insulin-like growth factor-1 expression in vascular endothelial cells by the inflammatory cytokine interleukin-1.

ABSTRACT

Insulin-like growth factor-1 (IGF-1) has important roles in vascular physiology and pathologies such as atherosclerosis. However, the factors that control expression of this growth factor in human vascular cells are largely unknown. In this study the effects of the inflammatory cytokine interleukin-1 (IL-1) on IGF-1 mRNA and peptide synthesis was examined in human endothelial cells. Cultured human umbilical vein endothelial (HUVE) cells were challenged with interleukin-1 and IGF-1 Ea and Eb mRNA levels were determined by nuclease protection assays and reverse transcription/polymerase chain reaction. IL-1 caused a dramatic increase in IGF-1 Ea mRNA in HUVE cells. Transcript levels peaked between 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 cells. These results demonstrate increased IGF-1 mRNA and peptide in vascular 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 promote the intimal hyperplasia often seen in these circumstances.