Desferrioxamine, an iron chelator, upregulates cyclooxygenase-2 expression and prostaglandin production in a human macrophage cell line.

Abstract

Prostaglandins (PGs) play regulatory roles in a variety of physiological and pathological processes, including the immune response, cytoprotection and inflammation. Desferrioxamine (DFX), an iron chelator, is known to reduce free radical-mediated cell injury and to upregulate certain inflammatory mediators. We investigated the effects of DFX on the production of PGs and the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGs, using a human macrophage cell line, U937. Our results showed that COX-2 expression and PGE(2) production are upregulated by DFX treatment and that this upregulation is dependent on both COX-2 promoter activity and alteration of mRNA stability. COX-2 promoter activity may be, at least in part, mediated by activation of the extracellular signal-regulated kinase pathway. These findings suggest that iron metabolism may regulate inflammatory processes by modulating PGs as well as other inflammatory mediators.

• Authors: K Tanji, T Imaizumi, T Matsumiya, H Itaya, K Fujimoto, X Cui, T Toki, E Ito, H Yoshida, K Wakabayashi, K Satoh
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1530 Issue 2-3 Pg. 227-35 (Feb 26 2001) ISSN: 0006-3002 [Print] Netherlands
• PMID: 11239825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Iron Chelating Agents
• Isoenzymes
• Membrane Proteins
• RNA, Messenger
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Mitogen-Activated Protein Kinases
• Deferoxamine
• Dinoprostone

Topics

• Binding Sites
• Cell Line
• Cyclooxygenase 2
• Deferoxamine (pharmacology)
• Dinoprostone (biosynthesis)
• Enzyme Stability
• Genes, Reporter
• Humans
• Iron Chelating Agents (pharmacology)
• Isoenzymes (biosynthesis, genetics)
• Macrophages (drug effects, metabolism)
• Membrane Proteins
• Mitogen-Activated Protein Kinases (metabolism)
• Promoter Regions, Genetic
• Prostaglandin-Endoperoxide Synthases (biosynthesis, genetics)
• RNA, Messenger (analysis, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation