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. Epub 2014 Jul 30.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Endoribonucleases / physiology*
  • Female
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Ribonucleases / physiology*
  • Urinary Tract / enzymology*
  • Urinary Tract / microbiology*

Substances

  • Endoribonucleases
  • RNase 6, mouse
  • Ribonucleases
  • Ribonuclease 7