title: Endogenous antimicrobial peptides and skin infections in atopic dermatitis.
abstract: BACKGROUND
  The innate immune system of human skin contains antimicrobial peptides known as cathelicidins (LL-37) and beta-defensins. In normal skin these peptides are negligible, but they accumulate in skin affected by inflammatory diseases such as psoriasis. We compared the levels of expression of LL-37 and human beta-defensin 2 (HBD-2) in inflamed skin from patients with atopic dermatitis and from those with psoriasis.
  
  
  METHODS
  The expression of LL-37 and HBD-2 protein in skin-biopsy specimens from patients with psoriasis, patients with atopic dermatitis, and normal subjects was determined by immunohistochemical analysis. The amount of antimicrobial peptides in extracts of skin samples was also analyzed by immunodot blot analysis (for LL-37) and Western blot analysis (for HBD-2). Quantitative, real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays were used to confirm the relative expression of HBD-2 and LL-37 messenger RNA (mRNA) in the skin-biopsy specimens. These peptides were also tested for antimicrobial activity against Staphylococcus aureus with the use of a colony-forming assay.
  
  
  RESULTS
  Immunohistochemical analysis confirmed the presence of abundant LL-37 and HBD-2 in the superficial epidermis of all patients with psoriasis. In comparison, immunostaining for these peptides was significantly decreased in acute and chronic lesions from patients with atopic dermatitis (P=0.006 and P=0.03, respectively). These results were confirmed by immunodot blot and Western blot analyses. Real-time RT-PCR showed significantly lower expression of HBD-2 mRNA and LL-37 mRNA in atopic lesions than in psoriatic lesions (P=0.009 and P=0.02, respectively). The combination of LL-37 and HBD-2 showed synergistic antimicrobial activity by effectively killing S. aureus.
  
  
  CONCLUSIONS
  A deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Peck Y
authors.initials: PY
authors.lastname: Ong
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ohtake
authors.forename: Corinne
authors.initials: C
authors.lastname: Brandt
authors.forename: Ian
authors.initials: I
authors.lastname: Strickland
authors.forename: Mark
authors.initials: M
authors.lastname: Boguniewicz
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054804:Cathelicidins; D002460:Cell Line; D003876:Dermatitis, Atopic / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins