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.
Valentine
J F
JF
Department of Medicine, University of Florida, Gainesville.
Nick
H S
HS
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D003300:Copper / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D004926:Escherichia coli; D016898:Interferon-alpha / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008070:Lipopolysaccharides; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016898:Interferon-alpha; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003300:Copper; D003513:Cycloheximide; D013482:Superoxide Dismutase