| Popis: |
Norcantharidin (NCTD) is a demethylated analogue of cantharidin. It was recently demonstrated that NCTD reduces iron contents in the liver and spleen of mice in vivo, indicating that NCTD can affect iron metabolism via hepcidin. Here, we investigated the effects of NCTD on expression of iron storage protein ferritin-light chain (Ft-L), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1), hepcidin, iron regulatory protein 1 (IRP1), IL-6, p-JAK2 and p-STAT3 in lipopolysaccharides (LPS)-treated RAW264.7 cells in vitro via Real-time PCR and Western blotting analysis. We demonstrate that NCTD down-regulates Ft-L, hepcidin, IL-6, pJAK2, pSTAT3 and up-regulates TfR1, DMT1, Fpn1 and IRP1 expression in LPS treated cells, showing that NCTD can inhibit hepcidin via the IL-6/JAK2/STAT3 signalling pathway and also increase TfR1, DMT1 and Fpn1 expression via down-regulating hepcidin and up-regulating IRP1. Our findings provide further evidence in vitro for the role of NCTD in iron metabolism. A hypothetical scheme for NCTD to affect the expression of iron transport, storage and regulatory proteins or mRNA in LPS-treated RAW264.7 cells. NCTD downregulates hepcidin by inhibiting the IL-6/JAK2/STAT3 signaling pathway and up-regulates Fpn1 via down-regulation of hepcidin. The upregulation of TfR1 and DMT1 expression is mainly induced by increased IRP1 expression. The positive effect of NCTD on Fpn1 may be more significant than its effect on TfR1 expression, leading to a reduced amount of iron intake relative to iron release and hence reduced Ft-L expression under inflammatory conditions. (Solid-line: a major (dominant) role, Dotted-line: a minor role). |
