Extracellular functions of thioredoxin.

Thioredoxin (TRX) is a small multifunctional protein with a redox-active dithiol/disulfide in the conserved active site. Human TRX was originally identified as a cytokine-like factor in virus-transformed cells. The TRX family of proteins share the active site sequence: -Cys-Xxx-Xxx-Cys-. Intracellularly TRX scavenges reactive oxygen species and regulates various signal transduction pathways in cellular activation and apoptosis. TRX is induced and released from cells in response to oxidative stress. TRX levels in plasma or serum are good markers for oxidative stress. Extracellularly, TRX shows anti-inflammatory effects. Circulating TRX in plasma inhibits neutrophil extravasation into the inflammatory sites. More recently we found that TRX inhibits the expression and release of macrophage migration inhibitory factor (MIF), which is a classical proinflammatory cytokine and a member of TRX family. Administration of recombinant TRX protein may become a novel therapeutic strategy for acute inflammatory disorders.