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.
Tanji
K
K
Department of Molecular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Japan. kunikazu@cc.hirosaki-u.ac.jp
Imaizumi
T
T
Matsumiya
T
T
Itaya
H
H
Fujimoto
K
K
Cui
X
X
Toki
T
T
Ito
E
E
Yoshida
H
H
Wakabayashi
K
K
Satoh
K
K
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