Thioredoxin Peroxidase (Natural Killer Enhancing Factor) Regulation of Activator Protein-1 Function in Endothelial Cells

Thioredoxin peroxidase-1 (TxP-1), originally cloned as natural killer enhancing factor-B, belongs to a highly conserved antioxidant family. Tumor necrosis factor-α (TNF) activates the expression of activator protein-1 (AP-1) responsive genes. We show here that over-expression of TxP-1 blocks TNF-induced AP-1 activation in endothelial ECV304 cells, which was demonstrated by three independent experimental protocols: electromobility shift assay with AP-1 oligonucleotide probe; reporter gene expression with AP-1 binding site, and interleukin-8 production, which is dependent on AP-1. These results are consistent with the role of TxP-1 as an antioxidant and the previous reports that TNF-induced reactive oxygen species were responsible for AP-1 activation.