Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response.
We have demonstrated a dramatic induction of manganese superoxide dismutase (Mn-SOD) mRNA levels in response to lipopolysaccharide (LPS), interleukin-1, and tumor necrosis factor in pulmonary epithelial cells. These stimuli had no effect on the corresponding mRNA levels for the copper/zinc (Cu/Zn)-SOD. Identical treatments of pulmonary fibroblast cells with LPS showed only minor changes in the Mn-SOD mRNA levels demonstrating a cell type-specific effect for this acute inflammatory mediator. Furthermore, we have shown that hyperoxia has no effect within 24 h on Mn-or Cu/Zn-SOD mRNA levels in either fibroblasts or epithelial cells. The induction of Mn-SOD mRNA levels by LPS is completely inhibited by actinomycin. Treatment of cells with cycloheximide causes an induction equal to that for LPS, whereas co-treatment with cycloheximide and LPS resulted in a "super induction." This data is strongly suggestive of an important role for the Mn-SOD in the acute inflammatory response.
Department of Pediatrics, College of Medicine, University of Florida, Gainesville 32610.
G A
GA
Visner
W C
WC
Dougall
J M
JM
Wilson
I A
IA
Burr
H S
HS
Nick
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007249:Inflammation; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D012486:Salmonella typhimurium; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide; D013482:Superoxide Dismutase