Truncated Thioredoxin Is a Mitogenic Cytokine for Resting Human Peripheral Blood Mononuclear Cells and Is Present in Human Plasma

Human thioredoxin (Trx) catalyzes intracellular disulfide reductions but has also co-cytokine activity with interleukins after leaderless secretion. A recombinant truncated form of thioredoxin with the 80 N-terminal residues (Trx80) was purified to homogeneity. We discovered that Trx80 by itself is...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-12, Vol.275 (48), p.37474-37480
Main Authors: Pekkari, Klas, Gurunath, Ramanathan, Arnér, Elias S.J., Holmgren, Arne
Format: Article
Language:English
Subjects:
Chromatography, Ion Exchange
Circular Dichroism
Cytokines - blood
Cytokines - isolation & purification
Cytokines - physiology
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Humans
Medicin och hälsovetenskap
Mitogens - blood
Mitogens - isolation & purification
Mitogens - physiology
Monocytes - cytology
thioredoxin
Thioredoxins - blood
Thioredoxins - isolation & purification
Thioredoxins - metabolism
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Summary:Human thioredoxin (Trx) catalyzes intracellular disulfide reductions but has also co-cytokine activity with interleukins after leaderless secretion. A recombinant truncated form of thioredoxin with the 80 N-terminal residues (Trx80) was purified to homogeneity. We discovered that Trx80 by itself is a potent mitogenic cytokine stimulating growth of resting human peripheral blood mononuclear cells. No effect was seen by Trx, but Trx80 at 50–100 nm induced cell proliferation of human peripheral blood mononuclear cells in serum-free synthetic medium, measured as [3H]thymidine incorporation after 72 h, with a maximum effect being comparable with that of 5 units/ml of interleukin-2. Trx80 lacked redox activity, but CD spectra suggested a secondary structure similar to Trx. Reduced Trx80 had anMr of 25,000, indicating that it is a dimer in solution. We also developed two different sandwich enzyme-linked immunosorbent assays that distinguish between full-length Trx and Trx80 and determined plasma levels of Trx and Trx80 in blood donors. The levels of Trx80 varied from 2 to 175 ng/ml; in comparison levels of Trx varied from 16 to 55 ng/ml without correlation to Trx80. In conclusion, the naturally occurring Trx80 is a novel mitogenic cytokine for normal resting human blood mononuclear cells.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M001012200