Impact of Species-Specific Lactoferricin Peptides on Macrophage-Associated Inflammatory Processes

Abstract

Inflammation is the body’s response to injury or infection and is important for elimination of the infecting agent and healing. However, prolonged inflammation can be damaging and may lead to the development of chronic inflammatory disorders. Recently, there has been growing interest in exploiting antimicrobial peptides (AMPs) that exhibit immunoregulatory activities for treatment of inflammatory diseases. In this study, we have investigated the immunomodulatory effects of the AMP, lactoferricin, from three different species, bovine, murine, and human, with subtle differences in their amino acid sequences. Macrophages, which are a key player in the induction and propagation of inflammation, were used as a cellular model to investigate the effects of species-specific lactoferricin peptides on inflammatory processes. Bovine lactoferricin was the only one of the three peptides studied that downregulated LPS-induced pro-inflammatory cytokines, TNF-α and IL-6 in both human and murine macrophages. Lactoferricin peptides regulated inflammation through targeting of LPS-activated NF-κB and MAPK signaling pathways. The ability of lactoferricin to downregulate a macrophage-mediated inflammatory response suggests potential for the development of this peptide as a novel immunotherapeutic agent.