Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity

摘要: Human beta-defensins (hBDs) are crucial factors of intrinsic immunity that function in the immunologic response to a variety invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization cell lysis due their highly cationic nature. These molecules participate antimicrobial defenses control adaptive innate every mammalian species produced by various types. The C-terminal 15-mer peptide within hBD3, designated as hBD3-3, was selected for study its cell- skin-penetrating activity, which induce anti-inflammatory activity lipopolysaccharide-treated RAW 264.7 macrophages. hBD3-3 penetrated both outer cells mouse skin short treatment period. Two other fragments showed poorer penetration compared hBD3-3. inhibited lipopolysaccharide-induced production inducible nitric oxide synthase, oxide, secretory cytokines, such interleukin-6 tumor necrosis factor concentration-dependent manner. Moreover, reduced interstitial infiltration polymorphonuclear leukocytes lung inflammation model. Further investigation also revealed downregulated nuclear kappa B-dependent directly suppressing degradation phosphorylated-IκBα downregulating active B p65. Our findings indicate may be conjugated with drugs interest ensure proper translocation sites, cytoplasm or nucleus, has ability used carrier, suggest potential approach effectively treat inflammatory diseases.