title: Staphylococcus aureus Induces Increased Serine Protease Activity in Keratinocytes.
abstract: Bacteria that reside on the skin can influence the behavior of the cutaneous immune system, but the mechanisms responsible for these effects are incompletely understood. Colonization of the skin by Staphylococcus aureus (S. aureus) is increased in atopic dermatitis and can result in increased severity of the disease. In this study, we show that S. aureus stimulates human keratinocytes to increase their endogenous protease activity, including specific increases in trypsin activity. This increased protease activity coincided with increased expression of mRNA for kallikreins (KLKs), with KLK6, 13, and 14 showing the greatest induction after exposure to S. aureus. Suppression of mRNA for these KLKs in keratinocytes by targeted small interfering RNA silencing before S. aureus exposure blocked the increase in protease activity. Keratinocytes exposed to S. aureus showed enhanced degradation of desmoglein-1 and filaggrin, whereas small interfering RNA for KLK6, KLK13, and KLK14 partially blocked this degradation. These data illustrate how S. aureus directly influences the skin barrier integrity by stimulating endogenous proteolytic activity and defines a previously unknown mechanism by which S. aureus may influence skin diseases.
authors.affiliation: Department of Dermatology, University of California, San Diego, California, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Williams
authors.affiliation: Department of Dermatology, University of California, San Diego, California, USA.
authors.forename: Teruaki
authors.initials: T
authors.lastname: Nakatsuji
authors.affiliation: Department of Dermatology, University of California, San Diego, California, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Sanford
authors.affiliation: Department of Dermatology, University of California, San Diego, California, USA.
authors.forename: Alison F
authors.initials: AF
authors.lastname: Vrbanac
authors.affiliation: Department of Dermatology, University of California, San Diego, California, USA. Electronic address: rgallo@ucsd.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051183:Desmoglein 1 / Q000378:metabolism; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007610:Kallikreins / Q000502:physiology; D015603:Keratinocytes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D057057:Serine Proteases / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000472:pathogenicity*
chemical_list: D051183:Desmoglein 1; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D057057:Serine Proteases; D007610:Kallikreins