REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I EXPRESSION IN VASCULAR ENDOTHELIAL-CELLS BY THE INFLAMMATORY CYTOKINE INTERLEUKIN-1

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.