The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss

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	The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss
	Yu, Heguo ; Dong, Jing ; Gu, Yihua ; Liu, Haiyan ; Xin, Aijie ; Shi, Huijuan ; Sun, Fei ; Zhang, Yonglian ; Lin, Donghai ; Diao, Hua ; Lin DH(林东海)
刊名	http://dx.doi.org/10.1074/jbc.M112.411884
	2013
关键词	MALE REPRODUCTIVE-TRACT ANTIMICROBIAL PEPTIDES IN-VIVO DISULFIDE BONDS INNATE IMMUNITY GENE CLUSTERS SEPTIC SHOCK TNF-ALPHA EXPRESSION LPS
英文摘要	National Basic Research Program of China [2007CB914304, 2009CB941702]; Natural Science Foundation of China [31101030, 31170717, 30900233, 91129713]; 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 beta-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-alpha 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.
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/89061]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Yu, Heguo,Dong, Jing,Gu, Yihua,et al. The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss[J]. http://dx.doi.org/10.1074/jbc.M112.411884,2013.
APA	Yu, Heguo.,Dong, Jing.,Gu, Yihua.,Liu, Haiyan.,Xin, Aijie.,...&林东海.(2013).The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss.http://dx.doi.org/10.1074/jbc.M112.411884.
MLA	Yu, Heguo,et al."The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss".http://dx.doi.org/10.1074/jbc.M112.411884 (2013).