title: RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin.
abstract: We analyzed healthy human skin for the presence of endogenous antimicrobial proteins that might explain the unusually high resistance of human skin against infections. A novel 14.5-kDa antimicrobial ribonuclease, termed RNase 7, was isolated from skin-derived stratum corneum. RNase 7 exhibited potent ribonuclease activity and thus may contribute to the well known ribonuclease activity of human skin. RNase 7 revealed broad spectrum antimicrobial activity against many pathogenic microorganisms and remarkably potent activity (lethal dose of 90% < 30 nm) against a vancomycin-resistant Enterococcus faecium. Molecular cloning from skin-derived primary keratinocytes and purification of RNase 7 from supernatants of cultured primary keratinocytes indicate that keratinocytes represent the major cellular source in skin and that RNase 7 is secreted. RNase 7 mRNA expression was detected in various epithelial tissues including skin, respiratory tract, genitourinary tract, and at a low level, in the gut. In addition to a constitutive expression, RNase 7 mRNA was induced in cultured primary keratinocytes by interleukin-1beta, interferon-gamma, and bacterial challenge. This is the first report demonstrating RNases as a novel class of epithelial inducible antimicrobial proteins, which may play an important role in the innate immune defense system of human epithelia.
authors.affiliation: Clinical Research Unit, Department of Dermatology, University Hospital Kiel, Schittenhelmstrasse 7, D-24105 Kiel, Germany.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Harder
authors.forename: Jens-Michael
authors.initials: JM
authors.lastname: Schroder
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001483:Base Sequence; D002478:Cells, Cultured; D016984:Enterococcus faecium / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides; D012333:RNA, Messenger / Q000235:genetics; D012260:Ribonucleases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000166:cytology / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D012333:RNA, Messenger; D012260:Ribonucleases; C470000:Ribonuclease 7