Thioredoxin negatively regulates p38 MAP kinase activation and IL-6 production by tumor necrosis factor-alpha

We examined the regulatory role of a reduction/oxidation (redox) control pr otein, thioredoxin (TRX), in tumor necrosis factor-alpha (TNF-alpha)-induce d p38 MAP kinase activation and p38 MAP kinase-mediated cytokine expression utilizing TRX-transfected murine L929 cells (TRX14). The results showed th at TNF-alpha-induced p38 MAP kinase activation and interleukin-6 (IL-6) pro duction by TRX 14 were less than those by the parental L cells and the cont rol transfected L cells (Neo-1). SB 203580 as the specific inhibitor for p3 8 MAP kinase activity inhibited TNF-alpha-induced IL-6 production by the pa rental L cells, indicating that TNF-alpha-activated p38 MAP kinase regulate s IL-6 production by the cell lines used in this study. These results showe d that overexpression of TRX negatively regulates p38 MAP kinase activation and p38 MAP kinase-mediated IL-6 production by TNF-alpha-stimulated cells, indicating that TRX is critical for p38 MAP kinase activation which regula tes cytokine expression. (C) 1999 Academic Press.