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Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis

作者:Peck Y. Ong, Takaaki Ohtake, Corinne Brandt, Ian Strickland, Mark Boguniewicz, Tomas Ganz, Richard L. Gallo, Donald Y.M. Leung · 发表于:New England Journal of Medicine · 年份:2002 · DOI:10.1056/nejmoa021481 · 被引用次数:1973 · 研究领域:Antimicrobial Peptides and Activities、Dermatology and Skin Diseases、Pediatric health and respiratory diseases

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 blo...