2. Academic Validation
  3. Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract

Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract

  • Kidney Int. 2015 Jan;87(1):151-61. doi: 10.1038/ki.2014.268.
Brian Becknell 1,  Tad E Eichler 2,  Susana Beceiro 3,  Birong Li 2,  Robert S Easterling 2,  Ashley R Carpenter 4,  Cindy L James 5,  Kirk M McHugh 6,  David S Hains 7,  Santiago Partida-Sanchez 3,  John D Spencer 1
Affiliations

Affiliations

  • 1 1] Division of Nephrology, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA [2] Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
  • 2 Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
  • 3 Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
  • 4 Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA.
  • 5 Mass Spec and Proteomic Facility, The Ohio State University, Columbus, Ohio, USA.
  • 6 1] Division of Anatomy, The Ohio State University College of Medicine, Columbus, Ohio, USA [2] Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
  • 7 Department of Pediatrics, Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
PMID: 25075772 DOI: 10.1038/ki.2014.268
Abstract

Recent evidence suggests antimicrobial Peptides protect the urinary tract from Infection. Ribonuclease 7 (RNase 7), a member of the RNase A superfamily, is a potent epithelial-derived protein that maintains human urinary tract sterility. RNase 7 expression is restricted to primates, limiting evaluation of its antimicrobial activity in vivo. Here we identified ribonuclease 6 (RNase 6) as the RNase A superfamily member present in humans and mice that is most conserved at the amino acid level relative to RNase 7. Like RNase 7, recombinant human and murine RNase 6 has potent antimicrobial activity against uropathogens. Quantitative Real-Time PCR and immunoblot analysis indicate that RNase 6 mRNA and protein are upregulated in the human and murine urinary tract during Infection. Immunostaining located RNase 6 to resident and infiltrating monocytes, macrophages, and neutrophils. Uropathogenic E. coli induces RNase 6 peptide expression in human CD14(+) monocytes and murine bone marrow-derived macrophages. Thus, RNase 6 is an inducible, myeloid-derived protein with markedly different expression from the epithelial-derived RNase 7 but with equally potent antimicrobial activity. Our studies suggest RNase 6 serves as an evolutionarily conserved antimicrobial peptide that participates in the maintenance of urinary tract sterility.

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