A synthetic MD-2 mimetic peptide attenuates lipopolysaccharide-induced inflammatory responses in vivo and in vitro

摘要: Myeloid differentiation protein-2 (MD-2), a secreted glycoprotein that binds to both lipopolysaccharide (LPS) and toll like receptor 4 (TLR4), contributes the fine ligand recognition signaling activation on LPS-induced inflammation. Here we synthesized novel MD-2 mimetic peptide (MDMP), derived from putative LPS-binding domain TLR4-binding of MD-2, found MDMP dose-dependently bound LPS inhibited LPS-activated Limulus amebocyte lysate (LAL). Pretreatment with dampened inflammatory responses in RAW264.7 cells, including down-regulation TLR4-MD-2 complex cell surface, suppression binding inhibition mitogen-activated protein kinase (MAPKs) nuclear factor kappa B (NF-kappaB) activation, reduction tumor necrosis factor-alpha (TNF-alpha) production. Further, vivo pretreatment markedly protected against acute lung injury liver injury, as indicated by notable lethality, TNF-alpha These results demonstrate attenuates vitro, suggests may be useful treatment inflammation associated LPS.