title: Expression and antimicrobial function of beta-defensin 1 in the lower urinary tract.
abstract: Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1(-/-)) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1(-/-) and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.
authors.affiliation: Section of Nephrology, Nationwide Children's Hospital, Columbus, Ohio, United States of America ; Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.forename: John David
authors.initials: JD
authors.lastname: Spencer
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Carpenter
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Aspinder
authors.initials: A
authors.lastname: Singh
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ploeger
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kline
authors.forename: Patrick
authors.initials: P
authors.lastname: Ellsworth
authors.forename: Birong
authors.initials: B
authors.lastname: Li
authors.forename: Ehrhardt
authors.initials: E
authors.lastname: Proksch
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Schwaderer
authors.forename: David S
authors.initials: DS
authors.lastname: Hains
authors.forename: Sheryl S
authors.initials: SS
authors.lastname: Justice
authors.forename: Kirk M
authors.initials: KM
authors.lastname: McHugh
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014551:Urinary Tract / Q000378:metabolism* / Q000382:microbiology*; D056689:Uropathogenic Escherichia coli / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; C406407:DEFB1 protein, human; C120555:Defb1 protein, mouse; D023083:beta-Defensins