THIOREDOXIN AS A POTENT COSTIMULUS OF CYTOKINE EXPRESSION

Reduction/oxidation (redox) processes have been implicated in various biologic processes, including signal transduction, gene expression, an d cell proliferation, Thioredoxin is one of the major redox-regulatory molecules which because of its dithiol/ disulfide exchange activity d etermines the oxidation state of protein thiols, in this study, we rep ort that treatment of several cell types with thioredoxin strongly enh ances the expression of various cytokines, In monocytic Mono Mac6 cell s stimulated with the phorbolester tetradecanoyl phorbolacetate (TPA), thioredoxin was found to augment the expression of TNF at the protein and mRNA levels, In this and other cell lines, such as fibrosarcoma a nd endothelial cells, thioredoxin also dose-dependently increased the synthesis of IL-6, Treatment of TPA-stimulated Mono Mac6 cells resulte d in a strong potentiation of secreted IL-1 bioactivity and expression of IL-1 alpha and IL-8 mRNA, In addition, in TPA-activated Molt-4 T c ells, an increased expression of IL-2 and IL-2-specific transcripts wa s detected, These data demonstrate that cytokine synthesis may be tigh tly controlled by redox-dependent processes, As thioredoxin is readily secreted and taken up by cells, it may play an important role as a co stimulatory molecule involved in immune processes.