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)-S...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-02, Vol.265 (5), p.2856-2864
Main Authors: VISNER, G. A, DOUGALL, W. C, WILSON, J. M, BURR, I. A, NICK, H. S
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Animals
Biological and medical sciences
Blotting, Northern
Cell Line
Cycloheximide - pharmacology
Dactinomycin - pharmacology
Dose-Response Relationship, Drug
Enzymes and enzyme inhibitors
Escherichia coli
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic - drug effects
Inflammation
Interleukin-1 - pharmacology
Kinetics
Lipopolysaccharides - pharmacology
Oxidoreductases
RNA, Messenger - drug effects
RNA, Messenger - genetics
Salmonella typhimurium
Superoxide Dismutase - biosynthesis
Superoxide Dismutase - genetics
Transcription, Genetic - drug effects
Tumor Necrosis Factor-alpha - pharmacology
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/s0021-9258(19)39880-1