title: Lipopolysaccharides upregulate hepcidin in neuron via microglia and the IL-6/STAT3 signaling pathway.
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.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Qian
authors.forename: Xuan
authors.initials: X
authors.lastname: He
authors.forename: Tuo
authors.initials: T
authors.lastname: Liang
authors.forename: Ka-Chun
authors.initials: KC
authors.lastname: Wu
authors.forename: Yik-Chun
authors.initials: YC
authors.lastname: Yan
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Lu
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Luo
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D064451:Hepcidins / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D064451:Hepcidins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor