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

	The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss
	Yu, HG; Dong, J; Gu, YH; Liu, HY; Xin, AJ; Shi, HJ; Sun, F; Zhang, YL; Lin, DH; Diao, H
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2013
卷号	288 期号:17 页码:12270-12282
通讯作者	Zhang, YL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai Key Lab Mol Androl,State Key Lab Mol Bio, Shanghai 200031, Peoples R China.,ylzhang@sibs.ac.cn ; dhlin@xmu.edu.cn ; diaohua@gmail.com
英文摘要	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.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	MALE REPRODUCTIVE-TRACT ; ANTIMICROBIAL PEPTIDES ; IN-VIVO ; DISULFIDE BONDS ; INNATE IMMUNITY ; GENE CLUSTERS ; SEPTIC SHOCK ; TNF-ALPHA ; EXPRESSION ; LPS
收录类别	SCI
语种	英语
WOS记录号	WOS:000318157600058
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/456]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yu, HG,Dong, J,Gu, YH,et al. The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(17):12270-12282.
APA	Yu, HG.,Dong, J.,Gu, YH.,Liu, HY.,Xin, AJ.,...&Diao, H.(2013).The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss.JOURNAL OF BIOLOGICAL CHEMISTRY,288(17),12270-12282.
MLA	Yu, HG,et al."The Novel Human beta-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss".JOURNAL OF BIOLOGICAL CHEMISTRY 288.17(2013):12270-12282.