Truncated thioredoxin (Trx80) induces production of interleukin-12 and enhances CD14 expression in human monocytes.
Human thioredoxin (Trx) is the major 12-kd cellular disulfide-reductase that on secretion acts as a cocytokine with several interleukins. Truncated Trx with the 80 N-terminal residues (Trx80), also present in plasma, was by itself a mitogenic cytokine for human peripheral blood mononuclear cells (PBMC). This study investigated which cells in PBMC are targets of recombinant Trx80. Purified human CD14(+) monocytes, but not B or T cells, in a synthetic medium were activated to differentiation by Trx80 as measured by flow cytometry of surface antigens because exposure to 100 nM Trx80 increased expression of CD14, CD40, CD54, and CD86. Proliferation of the monocytes was increased in a dose-dependent manner by Trx80 in concentrations ranging from 10 nM to 1 microM. Trx or interleukin (IL) 2 did not induce proliferation or expression of surface antigens on monocytes. Trx80 alone induced secretion of IL-12 from CD40(+) monocytes in the PBMC cultures and this effect was enhanced by IL-2. Trx80 and IL-2 together were strongly synergistic to induce secretion of interferon-gamma in PBMC cultures. The results showed that Trx80 is a potent cytokine for normal human monocytes and directs the immune system in favor of a Th1 response via IL-12 production.
Pekkari
K
K
Medical Nobel Institute for Biochemistry, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Avila-Cariño
J
J
Bengtsson
A
A
Gurunath
R
R
Scheynius
A
A
Holmgren
A
A
D015703:Antigens, CD / Q000032:analysis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C427943:Trx80 protein, human; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D013879:Thioredoxins; D007371:Interferon-gamma