Hepcidin protects sepsis through regulating iron homeostasis to inhibit immunocyte apoptosis in mice (P4435)

Abstract

Abstract Background: Hepcidin is a key regulator of iron metabolism and may have a critical role in modulating LPS-induced acute inflammatory responses. The role of hepcidin in cecal ligation and puncture (CLP) induced sepsis model was not clear. Methods: Adenovirus-mediated shRNA to inhibit the expression of hepcidin and a relative negative control were constructed and were administrated to mice through hydrodynamic injection via tail vein. Thirteen days later, the mice were subjected to CLP. Bacterial colony counts in blood and organs, reactive oxygen species (ROS) production in liver and immunocyte apoptosis in spleen were analyzed. Survival rate was estimated after 7 days. Results: The survival rate of hepcidin-knock down (KD) mice in CLP-induced sepsis was significantly decreased. Hepcidin-KD mice exposed to CLP showed more severe lung injury and increased inflammation cytokines. The serum iron concentration in hepcidin-KD mice after CLP was significantly higher, which resulted in more ROS production in liver and increased bacterial counts in blood and organs. In the spleen, there were significantly more apoptotic immunocytes in hepcidin-KD mice than those in controls. However, no significant differences in SOCS3 and phosphorylation of STAT3 level between the two groups were observed. Conclusions: Hepcidin may have a protective role in sepsis through regulating iron balance to inhibit bacterial infection and oxidative stress, which then protected immunocyte from apoptosis.