title: The novel human β-defensin 114 regulates lipopolysaccharide (LPS)-mediated inflammation and protects sperm from motility loss.
abstract: Lipopolysaccharide (LPS) is an important pathological factor involved in serious inflammatory diseases and male reproductive impairments. Emerging evidence demonstrates that antimicrobial peptides possess protective activity in response to LPS-induced inflammation. However, the LPS-binding and/or immunosuppressive activity of β-defensins (DEFBs) has been underestimated. In the present work, we characterized a novel human defensin, DEFB114, which was expressed predominantly in the epididymis and gingival cells at the RNA level. Homogenous recombinant DEFB114 peptides were prepared and characterized using mass spectrometry. DEFB114 protein exhibited a broad spectrum of antimicrobial activity with salt sensitivity against typical pathogenic microbes (i.e. Escherichia coli, Staphylococcus aureus, and Candida albicans). Interestingly, DEFB114 demonstrated novel LPS-binding activity in vitro and inhibited TNF-α release in RAW264.7 cultures through the inhibition of MAPK p42/44 when challenged with LPS. Moreover, DEFB114 could also rescue the LPS-induced reduction of human sperm motility in vitro and protect d-galactosamine-sensitized C57BL/6 mice from LPS-induced lethality in vivo. The protective activity of DEFB114 on RAW264.7, human sperm, and the d-galactosamine-sensitized mice was disulfide bond-dependent because alkylated DEFB114 lost its activity. The low cytotoxicity of the DEFB114 peptide toward human erythrocytes is indicative of its potential therapeutic use in the treatment of LPS-induced inflammation, LPS contamination, and potentially septic shock.
authors.affiliation: National Population and Family Planning Commission Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China.
authors.forename: Heguo
authors.initials: H
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Yihua
authors.initials: Y
authors.lastname: Gu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.forename: Aijie
authors.initials: A
authors.lastname: Xin
authors.forename: Huijuan
authors.initials: H
authors.lastname: Shi
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Yonglian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Donghai
authors.initials: D
authors.lastname: Lin
authors.forename: Hua
authors.initials: H
authors.lastname: Diao
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013081:Sperm Motility / Q000187:drug effects / Q000502:physiology*; D023083:beta-Defensins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D023083:beta-Defensins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3