Original Research ArticleAspirin increases ferroportin 1 expression by inhibiting hepcidin via the JAK/STAT3 pathway in interleukin 6-treated PC-12 cells

- IL-6 induces a severe decline in Fpn1 and cell viability and an increase in Ft-L.
- ASA abolishes the effects of IL-6 on Fpn1 an Ft-L expression and cell viability.
- IL-6 increases hepcidin expression and JAK2 and STAT3 phosphorylation.
- ASA suppresses the effects. IL-6 on the expression of hepcidin, p-JAK2 and p-STAT3.
- ASA increases Fpn1 by inhibiting hepcidin via a IL-6/JAK/STAT3 pathway.

To understand the potential mechanisms involved in the beneficial effects of aspirin (ASA) in mood disorders, Alzheimer's (AD) and Parkinson's disease (PD), we investigated the effects of ASA on the expression of iron transport proteins transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1), and iron storage protein ferritin light chain (Ft-L) in interleukin-6 (IL-6)-treated PC-12 cells. We demonstrated that IL-6 alone could induce a severe decline in Fpn1 expression and cell viability, and an increase in Ft-L protein, while ASA could markedly diminish the effects of IL-6 on these parameters. We also found that IL-6 significantly increased hepcidin expression and janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, while ASA also observably suppressed these IL-6-induced effects. The data imply that ASA increases Fpn1 expression by inhibiting hepcidin expression via the IL-6/JAK/STAT3 pathway and show that the reduced content of Ft-L is due to the increased Fpn1 and subsequent iron release in the cells. The reduction of iron in neuronal cells by the increased expression of Fpn1 might be partly associated with the beneficial effects of ASA on mood disorders, AD and PD.