Tetsuo Kawaguchi

Induction of Mn-superoxide dismutase by Tumor Necrosis Factor, Interleukin-1 and Interleukin-6 in human hepatoma cells

Effects of Tumor Necrosis Factor (TNF), Interleukin-1 (IL-1), Interleukin-6 (IL-6) and Interferon-gamma (IFN-gamma) on the expression of Mn-superoxide dismutase (Mn-SOD) protein were investigated in human hepatoma cells, Hu-H1, which revealed resistance to the cytotoxicity of TNF and IL-1. Both TNF and IL-1 enhanced the Mn-SOD production to the level of 30- to 40-fold. IL-6 also increased the enzyme protein to 2- to 3-fold of the basal level without any cell proliferative effect. A specific antibody against IL-6 almost completely inhibited the induction of Mn-SOD. IL-6, as well as TNF and IL-1, appears to play some role in the Mn-SOD protein expression in human hepatoma cells.

Stimulation of Mn-superoxide dismutase expression by tumor necrosis factor-α: Quantitative determination of Mn-SOD protein levels in TNF-resistant and sensitive cells by elisa☆

Marked increase in protein levels of Mn-superoxide dismutase (Mn-SOD) was found in TNF-resistant cell lines after treatment with Tumor Necrosis Factor (TNF). No such increase was observed in Cu,Zn-superoxide dismutase (Cu, Zn-SOD) protein in either TNF-resistant or sensitive cells. These results support the data that the Mn-SOD is one of the rescue proteins required for resistance to TNF cytotoxicity in these cell lines (Wong et al., Cell 58, 923-931, 1990). Mn-SOD was also responsive to TNF stimulation in KURAMOCHI, a human ovarian adenocarcinoma cell line. This may explain our previous result that Mn-SOD protein is highly expressed in epithelial ovarian cancer (Ishikawa et al. Cancer Res. 50, 2538-2542, 1990).

Elevated serum manganese superoxide dismutase in acute leukemias

We measured the serum levels of manganese-superoxide dismutase (Mn-SOD) in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Serum Mn-SOD level for normal subjects was 94.1 +/- 23.5 ng/ml (mean +/- S.D.), the levels for AML and ALL patients were 159.6 +/- 77.1 ng/ml and 154.4 +/- 77.0 ng/ml, respectively. The serum Mn-SOD levels were unrelated to individual intracellular Mn-SOD levels, but correlated well with serum lactate dehydrogenase values. Regression of the leukemia was accompanied by decrease in the serum level of Mn-SOD. Serum Mn-SOD may thus serve as a measure of the activity of the disease.

Reactivity of a monoclonal antibody to manganese superoxide dismutase with human ovarian carcinoma

A monoclonal antibody against manganese superoxide dismutase was assessed for its use in detecting a marker for epithelial ovarian carcinoma. An enzyme-linked immunosorbent assay indicated that less than 1% of normal individuals had serum levels over 150 ng per ml of serum, whereas over 50% of such patients showed elevated amounts. The serum levels of manganese superoxide dismutase correlated with the clinical stage of the disease and with the effects of therapy. The antibody used reacts with cryopreserved epithelial ovarian carcinomas but not with normal adult ovary or other normal tissues. Determination of the levels of this enzyme should provide a useful method for detection and monitoring of responses to treatment of epithelial ovarian carcinomas.