Human skin can defend itself against potentially invading microorganisms by production of antimicrobial peptides (AMPs). The expression of AMPs in atopic dermatitis (AD) is still emerging. To gain more insight into the role of AMPs in AD, we systematically analyzed the expression of ribonuclease 7 (RNase 7), psoriasin, and human beta-defensins (hBD)-2 and -3 in AD compared with psoriatic and healthy control skin as well as after experimental barrier disruption. Immunostaining revealed enhanced expression of all AMPs in the lesional skin of untreated AD and psoriasis when compared with non-lesional skin and controls. Accordingly, induced in vivo secretion of RNase 7, psoriasin, and hBD-2 was detected using ELISA on lesional skin in AD and in even higher concentrations in psoriasis. The secretion of AMPs did not correlate with severity of AD and Staphylococcus aureus colonization. Skin barrier disruption caused enhanced immunoreactivity of hBD-2 and hBD-3 after 24 hours. Strong secretion of RNase 7 was already detected after 1 hour, whereas hBD-2 secretion was significantly enhanced after 24 hours only under occlusion. Thus, a disturbed skin barrier may trigger AMP induction in AD and psoriasis. The functional role of AMP in AD, especially with regard to the control of S. aureus colonization, needs further analysis.
The innate defense of the skin against microbial threats is influenced by antimicrobial proteins (AMP). Staphylococcus aureus often colonizes the skin of patients with atopic dermatitis (AD). This was explained by diminished expression of AMP including cathelicidin/LL-37, human beta-defensins-2 and -3, and dermcidin. The S100-protein psoriasin is an additional keratinocyte-derived AMP that preferentially kills E. coli. As E. coli infections are not observed in atopic skin we investigated the functional role of psoriasin in AD patients. Immunohistochemistry demonstrated enhanced epidermal psoriasin expression in AD. An up to 1500-fold increase in secreted psoriasin was detected by ELISA in vivo on the surface of AD skin compared to healthy control skin. Surprisingly, tumor necrosis factor-alpha-enhanced psoriasin release in primary keratinocytes was inhibited by the Th2-cytokines IL-4 and -13, whereas IL-17 and -22 induced psoriasin. Epidermal barrier disruption significantly enhanced psoriasin expression as demonstrated by tape stripping in healthy volunteers. The upregulation of psoriasin in AD maybe induced by the disrupted skin barrier offering a possible explanation why these patients do not suffer from skin infections with E. coli. This indicates that the antimicrobial response in AD is not generally impaired, but greatly differs according to the type of AMP produced by the skin.
Skin wounds usually heal without major infections, although the loss of the mechanical epithelial barrier exposes the tissue to various bacteria. One reason may be the expression of antimicrobial peptides (AMP) of which some [human bdefensins (hBD) and were recently shown to support additionally certain steps of wound healing. There are no studies which have compared expression patterns of different classes of AMP in chronic wounds. The aim of our study was therefore to analyse the expression profile of hBD-2, hBD-3, LL-37, psoriasin and RNase 7 by immunohistochemistry from defined wound margins of chronic venous ulcers. We detected a strong induction of psoriasin and hBD-2 in chronic wounds in comparison with healthy skin. Except for stratum corneum, no expression of RNase 7 and LL-37 was detected in the epidermis while expression of hBD-3 was heterogeneous. Bacterial swabs identified Staphylococcus aureus and additional bacterial populations, but no association between colonization and AMP expression was found. The differential expression of AMP is noteworthy considering the high bacterial load of chronic ulcers. Clinically, supplementation of AMP with the capability to enhance wound healing besides restricting bacterial overgrowth could present a physiological support for treatment of disturbed wound healing.
Antimicrobial peptides (AMP) are key players in the skin's defense system. Previous observations suggest a site-and age-dependent expression of individual AMP. We investigated the expression and secretion patterns of four important AMP in a representative collective of healthy human skin samples. Levels of psoriasin, RNase 7 and hBD-3 expression -assessed by immunohistochemistry -varied between different body localisations. Older individuals expressed hBD-2 more frequently. No gender-related expression was observed. The in vivo secretion of psoriasin, measured in skin washing fluids using ELISA, was related to body localisation and age, whereas RNase 7 secretion showed no significant differences regarding these variables. HBD-2 and -3 secretion could not be detected. Our findings suggest the usage of control samples matching localisation and approximate age (in the case of hBD-2) for comparative immunohistochemical analysis. To avoid bias through great interindividual differences, sufficient large collectives should be used for in vivo secretion analyses.Abbreviations: AMP, antimicrobial peptides; ELISA, enzyme-linked immunosorbent assay; hBD, human b-defensin; IHC-Score, immunohistochemistry-Score; RNase, ribonuclease.
Despite permanent confrontation with a potentially harmful environment, its own microbiota and the fact that minor injuries occur frequently in everyday life, skin infections are a rare event. A chemical barrier of antimicrobial peptides (AMP), some of them constitutively expressed, others inducible by various stimuli, contributes to the integument's resistance. AMP are evolutionarily old components of the innate immunity which became the focus of interest due to their broad spectrum of activity against microorganisms and the rare occurrence of antimicrobial resistance. These attributes make them promising alternative candidates for future antibiotics. Furthermore various dermatological diseases are associated with an altered expression of these molecules, which might then play a pathogenetic role. In addition to their antimicrobial activity, some AMP have immunomodulatory effects and can promote wound healing, properties which currently are under intensive research.
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