Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism.

摘要: Cathelicidins are a family of gene-encoded peptide effectors innate immunity found exclusively in vertebrates. They play pivotal roles host immune defense against microbial invasions. Dozens cathelicidins have been identified from several vertebrate species. However, no cathelicidin marine reptiles has characterized previously. Here we report the identification and characterization novel (Hc-CATH) sea snake Hydrophis cyanocinctus. Hc-CATH is composed 30 amino acids, sequence KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy structure modeling analysis indicated that mainly assumes an amphipathic α-helical conformation bacterial membrane-mimetic solutions. It possesses potent broad-spectrum rapid antimicrobial activity. Meanwhile, it highly stable shows low cytotoxicity toward mammalian cells. The killing activity executed through disruption cell membrane lysis In addition, exhibited anti-inflammatory by inhibiting LPS-induced production nitric oxide (NO) pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6. directly binds with LPS to neutralize its toxicity, also Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits binding TLR4/MD2 complex subsequent activation inflammatory response pathways. Taken together, our study demonstrates Hc-CATH, first discovered both activity, candidate for development antibiotics.