Acute-phase Induction of Manganese Superoxide Dismutase in Intestinal Epithelial Cell Lines

Cellular protection from immune-generated oxygen free radicals is initiated by the reduction of oxygen radicals by manganese superoxide dismutase (MnSOD) and copper/zinc superoxide dismutase (Cu/ZnSOD). Using rat adult (IEC-6) and fetal (IRD-98) intestinal epithelial cell lines, factors involved in the regulation of the SODs at the messenger RNA (mRNA) level were examined. Exposure of IEC-6 and IRD-98 to Escherichia coli lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-alpha) results in a marked increase in MnSOD mRNA as early as at 1 hour. Cotreatment of cells exposed to LPS or TNF-alpha with actinomycin D or cycloheximide showed that de novo transcription but not protein synthesis is required for the LPS- and TNF-alpha-dependent induction in MnSOD mRNA. Treatment with interleukin 1 beta results in a 12-fold increase in MnSOD mRNA, but no change was observed with interleukin 6 or interferon alpha. No change was observed in the level of Cu/ZnSOD mRNA under any condition tested. The results indicate that MnSOD functions as a cytokine-regulated acute phase protein involved in cellular protection from free radical-mediated damage.