Endogenous antimicrobial peptides and skin infections in atopic dermatitis
Endogenous antimicrobial peptides and skin infections in atopic dermatitis
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DOI：
10.1056/nejmoa021481
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发表时间：
2002-10-10
影响因子：
158.5
通讯作者：
Leung, DYM
中科院分区：
文献类型：
--
作者：
Ong, PY;Ohtake, T;Leung, DYM
背景：人类皮肤的先天免疫系统含有称为凯萨林菌素（LL-37）和（β）-防御素的抗菌肽。在正常皮肤中，这些肽可以忽略不计，但它们在受炎症性疾病如牛皮癣影响的皮肤中积累。我们比较了LL-37和人类（β）-防御素2（HBD-2）在异位性皮炎患者和银屑病患者的炎症皮肤中的表达水平。方法：LL-37和HBD-2蛋白在银屑病患者、异位性皮炎患者和正常人皮肤活检标本中的表达通过免疫组化分析进行测定。还通过免疫斑点印迹分析（对于LL-37）和蛋白质印迹分析（对于HBD-2）分析皮肤样品提取物中的抗微生物肽的量。定量，实时逆转录聚合酶链反应（RT-PCR）测定用于确认HBD-2和LL-37信使RNA（mRNA）在皮肤活检标本中的相对表达。这些肽也进行了测试，对金黄色葡萄球菌的抗菌活性与使用的菌落形成assay.Results：免疫组化分析证实了丰富的LL-37和HBD-2的存在下，在所有银屑病患者的表皮浅。相比之下，这些肽的免疫染色显着减少，在急性和慢性病变的特应性皮炎患者（P=0.006和P=0.03，分别）。这些结果通过免疫斑点印迹和Western印迹分析证实。荧光定量RT-PCR显示HBD-2 mRNA和LL-37 mRNA在特应性皮损中的表达显著低于银屑病皮损（P=0.009和P=0.02）。LL-37和HBD-2的组合通过有效地杀灭S. aureus.Conclusions:抗微生物肽表达的缺陷可能是特应性皮炎患者对皮肤S.金黄色。
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.