Different Characteristics of Hepcidin Expression in IL-6+/+ and IL-6-/- Neurons and Astrocytes Treated with Lipopolysaccharides

Neurochem Res. 2018 Aug;43(8):1624-1630. doi: 10.1007/s11064-018-2577-9. Epub 2018 Jun 19.

Abstract

A region-specific regulation of inflammation on the expression hepcidin in the brain has been demonstrated, however, it remains unknown whether there is also a cell-specific regulation of inflammation on hepcidin in the brain. Here, we investigated the effects of lipopolysaccharides (LPS) on the expression of hepcidin mRNA and also the expression of IL-6 mRNA, the phosphorylation of STAT3 and the expression of ferroportin 1 (Fpn1) and ferritin light chain (Ft-L) proteins in neurons and astrocytes obtained from wild type (IL-6+/+) and IL-6 knockout (IL-6-/-) mice. We demonstrated that the responses of the expression of hepcidin and IL-6 mRNAs, the phosphorylation of STAT3, and the expression of Fpn1 protein to LPS in IL-6+/+ astrocytes and also the responses of the expression of hepcidin mRNA, the phosphorylation of STAT3 and the expression of Fpn1 protein to IL-6 in IL-6-/- astrocytes were much stronger than those in IL-6+/+ and IL-6-/- neurons. A significant increase in Ft-L was found in LPS-treated IL-6+/+ and IL-6-treated IL-6-/- astrocytes, but not in LPS-treated IL-6+/+ and IL-6-treated IL-6-/- neurons. Our findings provide in vitro evidence for the existence of a cell-specific regulation of LPS on the expression of hepcidin and also Ft-L in the brain.

Keywords: Ferritin light chain (Ft-L) and cell iron content; Hepcidin and ferroportin 1 (Fpn1); IL-6/STAT3 pathway; Lipopolysaccharides (LPS); Neuron and astrocyte.

MeSH terms

  • Animals
  • Apoferritins / metabolism
  • Astrocytes / drug effects*
  • Cation Transport Proteins / metabolism
  • Gene Knockout Techniques
  • Hepcidins / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice, Inbred C57BL
  • Neurons / drug effects*
  • STAT3 Transcription Factor / metabolism

Substances

  • Cation Transport Proteins
  • Hepcidins
  • Interleukin-6
  • Lipopolysaccharides
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • interleukin-6, mouse
  • metal transporting protein 1
  • Apoferritins