Hepcidin-1 in olive flounder (Paralichthys olivaceus): Gene expression, antimicrobial and therapeutic effects of synthetic peptides against bacterial and viral infections

Abstract

Hepcidin is known to play an important role in iron metabolism and innate immunity as both a major regulator of iron homeostasis and, an antimicrobial peptide. In this study, we attempted to characterize the transcriptional and antimicrobial properties of hepcidin-1 in olive flounder (OF-hepcidin-1). Briefly, the gene expression level of OF-hepcidin-1 in olive flounder infected with viral hemorrhage septicemia virus (VHSV), Streptococcus parauberis, and Edwardsiella piscicida was quantified using real-time polymerase chain reaction (PCR) analysis. The antimicrobial activity and therapeutic effects of synthetic OF-hepcidin-1 were tested against several fish pathogens. The results showed that the expression of OF-hepcidin-1 mRNA was dramatically elevated in the liver, spleen, head kidney, and blood of infected olive flounder from 6 h post-challenge (hpc) to 7 days post-challenge (dpc), thus indicating its important role in innate immunity. Of note, a 133-fold increase in OF-hepcidin-1 mRNA was found in the blood of fish infected with VHSV at 6 hpc, while the VHSV concentration in the blood was near the border of detection limit; this indicates that OF-hepcidin-1 mRNA could be potentially used as an early infection bioindicator. OF-hepcidin-1 gene expression was significantly correlated with OF-IL-6 expression (p < 0.05), indicating that IL-6 might be closely involved in hepcidin expression in fish. Synthetic OF-hepcidin-1 exhibited antimicrobial activity against various fish pathogens including VHSV at a minimum dose of 50 μM fish−1. Further, OF-hepcidin-1 treatment in olive flounder infected with S. parauberis and VHSV showed a significantly lower infection rate and mortality (relative survival rate of 22.2% and 36.4%, respectively) than the control group, which suggests its potential usefulness in disease control applications.