title: Expression and Significance of the HIP/PAP and RegIIIγ Antimicrobial Peptides during Mammalian Urinary Tract Infection.
abstract: Recent evidence indicates that antimicrobial peptides (AMPs) serve key roles in defending the urinary tract against invading uropathogens. To date, the individual contribution of AMPs to urinary tract host defense is not well defined. In this study, we identified Regenerating islet-derived 3 gamma (RegIIIγ) as the most transcriptionally up-regulated AMP in murine bladder transcriptomes following uropathogenic Escherichia coli (UPEC) infection. We confirmed induction of RegIIIγ mRNA during cystitis and pyelonephritis by quantitative RT-PCR. Immunoblotting demonstrates increased bladder and urinary RegIIIγ protein levels following UPEC infection. Immunostaining localizes RegIIIγ protein to urothelial cells of infected bladders and kidneys. Human patients with UTI have increased urine concentrations of the orthologous Hepatocarcinoma-Intestine-Pancreas / Pancreatitis Associated Protein (HIP/PAP) compared to healthy controls. Recombinant RegIIIγ protein does not demonstrate bactericidal activity toward UPEC in vitro, but does kill Staphylococcus saprophyticus in a dose-dependent manner. Kidney and bladder tissue from RegIIIγ knockout mice and wild-type mice contain comparable bacterial burden following UPEC and Gram-positive UTI. Our results demonstrate that RegIIIγ and HIP/PAP expression is induced during human and murine UTI. However, their specific function in the urinary tract remains uncertain.
authors.affiliation: Division of Nephrology, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.|Center for Clinical and Translational Research, Research Institute at Nationwide Children's, Columbus, Ohio, United States of America.
authors.forename: John David
authors.initials: JD
authors.lastname: Spencer
authors.affiliation: Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Jackson
authors.affiliation: Center for Clinical and Translational Research, Research Institute at Nationwide Children's, Columbus, Ohio, United States of America.
authors.forename: Birong
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of Urology, Department of Surgery, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
authors.forename: Christina B
authors.initials: CB
authors.lastname: Ching
authors.affiliation: Department of Pediatrics and Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Vonau
authors.affiliation: Medical College of Ohio, Toledo, Ohio, United States of America.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Easterling
authors.affiliation: Division of Nephrology, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.|Center for Clinical and Translational Research, Research Institute at Nationwide Children's, Columbus, Ohio, United States of America.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Schwaderer
authors.affiliation: Department of Anatomy, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.|Center for Molecular and Human Genetics, Research Institute at Nationwide Children's, Columbus, Ohio, United States of America.
authors.forename: Kirk M
authors.initials: KM
authors.lastname: McHugh
authors.affiliation: Division of Nephrology, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.|Center for Clinical and Translational Research, Research Institute at Nationwide Children's, Columbus, Ohio, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D003556:Cystitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000073718:Pancreatitis-Associated Proteins; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D057790:Staphylococcus saprophyticus / Q000187:drug effects; D059467:Transcriptome; D001743:Urinary Bladder / Q000378:metabolism; D014552:Urinary Tract Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000187:drug effects; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D023181:Antimicrobial Cationic Peptides; D000073718:Pancreatitis-Associated Proteins; D010455:Peptides; C000612141:REG3A protein, human; D011994:Recombinant Proteins; C539690:proIslet peptide, human; D012313:RNA