Desferrioxamine, an iron chelator, upregulates cyclooxygenase-2 expression and prostaglandin production in a human macrophage cell line.
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.
Department of Molecular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Japan. kunikazu@cc.hirosaki-u.ac.jp
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K
Tanji
T
T
Imaizumi
T
T
Matsumiya
H
H
Itaya
K
K
Fujimoto
X
X
Cui
T
T
Toki
E
E
Ito
H
H
Yoshida
K
K
Wakabayashi
K
K
Satoh
D001665:Binding Sites; D002460:Cell Line; D051546:Cyclooxygenase 2; D003676:Deferoxamine / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D004795:Enzyme Stability; D017930:Genes, Reporter; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D007502:Iron Chelating Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020928:Mitogen-Activated Protein Kinases; D003676:Deferoxamine; D015232:Dinoprostone