Lipopolysaccharides Upregulate Hepcidin in Neuron via Microglia and the IL-6/STAT3 Signaling Pathway
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- 作者：Zhong-Ming Qian (1)
Xuan He (2)
Tuo Liang (2)
Ka-Chun Wu (2)
Yik-Chun Yan (2)
Li-Na Lu (2)
Guang Yang (1)
Qian Qian Luo (1)
Wing-Ho Yung (2)
Ya Ke (2) - 关键词：Hepcidin ; Brain iron ; Ferroportin 1 (Fpn1) ; Lipopolysaccharides (LPS) ; Interleukin ; 6 (IL ; 6) ; Signal transducer and activator of transcription 3 (STAT3) ; Cortex ; Substantia nigra
- 刊名：Molecular Neurobiology
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：50
- 期：3
- 页码：811-820
- 全文大小：2,146 KB
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17. Ganz T, Nemeth E (2011) Hepcidin and disorders of iron metabolism. Annu Rev Med 62:347-60- 作者单位：Zhong-Ming Qian (1)
Xuan He (2)
Tuo Liang (2)
Ka-Chun Wu (2)
Yik-Chun Yan (2)
Li-Na Lu (2)
Guang Yang (1)
Qian Qian Luo (1)
Wing-Ho Yung (2)
Ya Ke (2)
1. Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai, 201203, China
2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China- ISSN：1559-1182
- 作者单位：Zhong-Ming Qian (1)
文摘
Neuroinflammation is closely related to brain iron homeostasis. Our previous study demonstrated that lipopolysaccharides (LPS) can regulate expression of iron-regulatory peptide hepcidin; however, the mechanism is undefined. Here, we demonstrated that intracerebroventricular injection of LPS in rat brain upregulated hepcidin and downregulated ferroportin 1 in the cortex and substantia nigra. LPS increased hepcidin expression in neurons only when they were co-cultured with BV-2 microglia, and the upregulation was suppressed by IL-6 neutralizing antibody in vitro. In addition, IL-6 but not IL-1α, IL-1β, or tumor necrosis factor-alpha increased hepcidin expression and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cortical neurons and MES23.5 dopaminergic neurons. These effects were blocked by the STAT3 inhibitor, stattic. Our results show that neurons are the major source of increased hepcidin expression in response to LPS challenge but microglia play a key mediator role by releasing IL-6 and recruiting the STAT3 pathway. We conclude that LPS upregulates hepcidin expression in neurons via microglia and the IL-6/STAT3 signaling pathway.