LPS triggers inflammation response in periphery, whether the infection in CNS induced by LPS ICV injection affected the peripheral iron metabolism was unknown , The current study was to find out whether LPS injected to the brain could regulate hepcidin expression in liver and peripheral iron metabolism.
Wide type mice (IL-6+/+) and IL-6-/- mice of 8-week-old were performed on ICV injection with LPS. After 6h, hepcidin expression in liver, as well as serum iron and transferrin saturation was detected and calculated, we also tested the IL-6/JAK2/STAT3 pathway in hepcidin regulation in liver of IL-6 knockout (IL-6-/- mice) and IL-6+/+ mice, AG490 as an inhibitor of JAK2 was used to confirm the effect of IL-6/JAK2/STAT3 pathway on hepcidin expression in liver.
Hepcidin mRNA, IL-6 mRNA and protein expression in the liver of IL-6-/- mice was significantly lower than IL-6+/+ mice after LPS administration. IL-6 deficiency abolished the decrease of serum iron, transferrin saturation induced by LPS injection. IL-6 deficiency also abolished the decrease of Fpn1, increase of pSTAT3 and Ft-L protein in liver. AG490 significantly reduced the pSTAT3 protein and abolished the changes of Fpn1 and Ft-L expression induced by LPS in liver.
These finding provided further evidence that the effect of central inflammation on the hepatic hepcidin expression and peripheral iron metabolism.