Proteasome inhibitors stimulate activator protein-1 pathway via reactive oxygen species production
Journal
FEBS Letters
Journal Volume
526
Journal Issue
44199
Pages
101-105
Date Issued
2002
Author(s)
Abstract
In this report we explored the effects of proteasome inhibitors (MG132, aLLN, lactacystin and MG262) on interleukin-8 (IL-8) induction. In HEK293 cells, proteasome inhibitors could concentration-dependently increase IL-8 promoter and activator protein-1 (AP-1) activities, but inhibited nuclear factor (NF)-kappa B activation induced by cytokines. The stimulating effects on IL-8 promoter and AP-1 were reduced by N-acetylcysteine, glutathione, diphenyleneiodonium, rotenone and antimycin A. Fluorescent analysis using 2',7'-dichlorodihydrofluorescin diacetate further confirmed the abilities of proteasome inhibitors to induce reactive oxygen species (ROS) production. These results suggest that ROS production by proteasome inhibitors leads to AP-1 activation, which in the absence of NF-kappa B activation still transactivates IL-8 gene expression.
Type
journal article