K. Pekkari et al., Truncated thioredoxin is a mitogenic cytokine for resting human peripheralblood mononuclear cells and is present in human plasma, J BIOL CHEM, 275(48), 2000, pp. 37474-37480
Human thioredoxin (Trx) catalyzes intracellular disulfide reductions but ha
s 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 s
erum-free synthetic medium, measured as [H-3]thymidine incorporation after
72 h, with a maximum effect being comparable with that of 5 units/ml of int
erleukin-a. Trx80 lacked redox activity, but CD spectra suggested a seconda
ry structure similar to Trx. Reduced Trx80 had an M-r of 25,000, indicating
that it is a dimer in solution. We also developed two different sandwich e
nzyme-linked immunosorbent assays that distinguish between full-length Trx
and Trx80 and determined plasma levels of Trx and Trx80 in blood donors. Th
e levels of Trx80 varied from 2 to 175 ng/ml; in comparison levels of Trx v
aried 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.