LFP-20, a porcine lactoferrin peptide, ameliorates LPS-induced inflammation via the MyD88/NF-κB and MyD88/MAPK signaling pathways.

LFP-20 is one of the 20 amino acid anti-microbial peptides identified in the N terminus of porcine lactoferrin. Apart from its extensively studied direct anti-bacterial activity, its potential as an activator of immune-related cellular functions is unknown. Therefore, this study investigated its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated pig alveolar macrophages in vitro and systemic inflammation in an in vivo mouse model. We found that the inhibitory effects of LFP-20 on production of pro-inflammatory cytokines were independent of its LPS-binding activity. However, they were associated with NF-κB and MAPK-dependent signaling. Furthermore, LFP-20 might directly influence MyD88 levels to block its interaction with NF-κB and MAPK-dependent signaling molecules that might alter LPS-mediated inflammatory responses in activated macrophages. Taken together, our data indicated that LFP-20 prevents the LPS-induced inflammatory response by inhibiting MyD88/NF-κB and MyD88/MAPK signaling pathways, and sheds light on the potential use of LFP-20 in the therapy of LPS-mediated sepsis.