Iron homeostasis in astrocytes and microglia is differentially regulated by TNF-α and TGF-β1

被引:116
作者
Rathore, Khizr I. [1 ]
Redensek, Adriana [1 ]
David, Samuel [1 ]
机构
[1] McGill Univ, Ctr Hlth, Res Inst, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada
基金
加拿大健康研究院;
关键词
inflammation; neurodegeneration; iron; ferroportin; ceruloplasmin; ferritin; glia; SPINAL-CORD-INJURY; EPITHELIAL-MESENCHYMAL TRANSITION; MESSENGER-RNA; INFLAMMATORY RESPONSE; HUNTINGTONS-DISEASE; MULTIPLE-SCLEROSIS; OXIDATIVE STRESS; BRAIN IRON; FERRITIN; CERULOPLASMIN;
D O I
10.1002/glia.22303
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Abnormal iron homeostasis is increasingly thought to contribute to the pathogenesis of several neurodegenerative disorders. We have previously reported impaired iron homeostasis in a mouse model of spinal cord injury and in a mouse model of amyotrophic lateral sclerosis. Both these disorders are associated with CNS inflammation. However, what effect inflammation, and in particular, inflammatory cytokines have on iron homeostasis in CNS glia remains largely unknown. Here we report that the proinflammatory cytokine TNF-a, and the anti-inflammatory cytokine TGF-beta 1 affect iron homeostasis in astrocytes and microglia in distinct ways. Treatment of astrocytes in vitro with TNF-a induced the expression of the iron importer divalent iron transporter 1 (DMT1) and suppressed the expression of the iron exporter ferroportin (FPN). However, TGF-beta 1 had no effect on DMT1 expression but increased the expression of FPN in astrocytes. In microglia, on the other hand, both cytokines caused induction of DMT1 and suppression of FPN expression. Iron influx and efflux assays in vitro confirmed that iron homeostasis in astrocytes and microglia is differentially regulated by these cytokines. In particular, TNF-a caused an increase in iron uptake and retention by both astrocytes and microglia, while TGF-beta 1 promoted iron efflux from astrocytes but caused iron retention in microglia. These data suggest that these two cytokines, which are expressed in CNS inflammation in injury and disease, can have profound and divergent effects on iron homeostasis in astrocytes and microglia. (C) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:738 / 750
页数:13
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