Lipopolysaccharides Upregulate Hepcidin in Neuron via Microglia and the IL-6/STAT3 Signaling Pathway

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Zhong-Ming Qian
  • Xuan He
  • Tuo Liang
  • Ka-Chun Wu
  • Yik-Chun Yan
  • Li-Na Lu
  • Guang Yang
  • Qian Qian Luo
  • Ya Ke

Detail(s)

Original languageEnglish
Pages (from-to)811-820
Journal / PublicationMolecular Neurobiology
Volume50
Issue number3
Publication statusPublished - 1 Dec 2014
Externally publishedYes

Abstract

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. © 2014, Springer Science+Business Media New York.

Research Area(s)

  • Brain iron, Cortex, Ferroportin 1 (Fpn1), Hepcidin, Interleukin-6 (IL-6), Lipopolysaccharides (LPS), Signal transducer and activator of transcription 3 (STAT3), Substantia nigra

Bibliographic Note

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Citation Format(s)

Lipopolysaccharides Upregulate Hepcidin in Neuron via Microglia and the IL-6/STAT3 Signaling Pathway. / Qian, Zhong-Ming; He, Xuan; Liang, Tuo et al.
In: Molecular Neurobiology, Vol. 50, No. 3, 01.12.2014, p. 811-820.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review