Pamela Urrutia, Pabla Aguirre, Andrés Esparza, Victoria Tapia, Natalia P. Mena, Miguel Arredondo, Christian González-Billault and Marco T. Núñez Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells Journal of Neurochemistry 126
Inflammation and iron accumulation are present in a variety of neurodegenerative diseases including Alzheimer's and Parkinson's disease. We analyzed the effects of the inflammatory cytokines TNF-α and Il-6 and of LPS on total cell iron content and on the expression and abundance of the iron transporters DMT1 and FPN1 in neurons, astrocytes, and microglia. Inflammatory stimuli increased expression of DMT1 in neurons, astrocytes, and microglia, induced the expression of hepcidin in astrocytes and microglia but not in neurons. Incubation with hepcidin transiently decreased the expression of FPN1 in the three cell types. The net result of these changes was increased iron accumulation in neurons and microglia but not in astrocytes. The findings establish a causal association between inflammation and iron accumulation in brain cells, presumably by changes in DMT1 and FPN1 expression and mediated in part by hepcidin.
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