Truncated thioredoxin: physiological functions and mechanism.
Human cytosolic thioredoxin (Trx), which is the 12-kDa protein disulfide reductase with the Cys-Gly-Pro-Cys active site and a key component of cellular redox biochemistry and regulation, acts as cocytokine upon leaderless secretion. A 10-kDa C-terminally truncated thioredoxin (Trx80) comprising the 80 or 84 N-terminal amino acids is also secreted and present in plasma, where it originally was purified and identified as eosinophilic cytotoxicity enhancing factor. Recombinant Trx80 was discovered to be a potent mitogenic cytokine that stimulates growth of resting human peripheral blood mononuclear cells (PBMC) in a synthetic medium, an effect that Trx lacks. Trx80 is very different from Trx because it is a dimer lacking reductase activity and the cytokine activity is not dependent on the Cys residues of the Trx active-site motif. The primary targets of Trx80 in PBMC are monocytes that are activated to proliferate and increase expression of CD14, CD40, CD54, and CD86. Trx80 induces secretion of interleukin (IL)-12 in CD40+ monocytes from PBMC. Trx80 and IL-2 together were strongly synergistic to induce secretion of interferon-gamma in PBMC. Trx80 is a potent cytokine for monocytes directing the immune system to a Th1 response via IL-12 production.
Pekkari
Klas
K
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Holmgren
Arne
A
D000595:Amino Acid Sequence; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism
D010446:Peptide Fragments; C427943:Trx80 protein, human; D013879:Thioredoxins