The Antimicrobial Protein Psoriasin (S100A7) Is Upregulated in Atopic Dermatitis and after Experimental Skin Barrier Disruption

Abstract

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 Barrier Dysfunction and Low Antimicrobial Peptide Expression in Cutaneous T-cell Lymphoma

“…Table 1. Filaggrin, loricrin, S100A7, and S100A8 expression in lesional skin of patch, plaque, tumor, erythroderma of CTCL, atopic dermatitis, psoriasis and in normal skin filaggrin loricrin S100A7 S100A8 Normal 5 0% 40% 60% 0% 40% 60% 80% 20% 0% 80% 20% 0% CTCL (patch) 5 20% 60% 20% 40% 60% 0% 60% 40% 0% 40% 60% 0% CTCL (plaque) 5 60% 40% 0% 60% 40% 0% 60% 40% 0% 60% 20% 20% CTCL (tumor) 5 80% 20% 0% 80% 20% 0% 60% 40% 0% 40% 60% 0% CTCL (erythroderma) 5 80% 20% 0% 60% 40% 0% 80% 20% 0% 60% 40% 0% Atopic dermatitis 5 80% 20% 0% 80% 20% 0% 40% 60% 0% 60% 40% 0% Psoriasis 5 80% 20% 0% 80% 20% 0% 0% 40% 60% 0% 40% (44)(45)(46). Consistently, in CTCL lesional skin, we detected significant negative correlations between expression levels of S100A7 and those of CCL26 or CCR3, a representative T H 2 chemokine/chemokine receptor pair (Fig.…”

The role of IL-36γ/IL-1F9 in developing erythroderma in patients with psoriasis

“…К сожалению, некоторые из этих маркёров, такие как протеины S100 А7, А8 и А9, экспрессируются не только при псори-азе [25,33], но также в случае других воспали-тельных кожных заболеваний [16,29]. В работах M. Nold и соавт.…”

“…(2013) показана увеличенная экс-прессия IL-36γ в коже у пациентов с псориазом (n=38 и n=17) [20]. В отличие от других маркё-ров, описанных раннее при псориазе, например S100 А7, А8 и А9 [16,23,25,33], маркёр IL-36γ ока-зался высокоспецифичным для псориаза (при других воспалительных заболеваниях кожи, в том числе атопическом дерматите и контактной экземе, экспрессия выражена слабо) [20].…”

The role of antimicrobial peptides in chronic inflammatory skin diseases

“…Researches revealed a lower expression of hBD-2, hBD-3 and LL-37 in the skin of patients with AD when compared to psoriasis vulgaris [44,45]. A possible explanation could be the lack of major inducers in the AD skin, such as IL-1, IL-17 and IL-22, alongside with inhibition of AMPs induction by an elevated level of Th2 cytokines (IL-4, IL-10 and IL-13) [46]. However, the observation of AMPs in AD was based on the comparison to the lesional psoriatic skin, and not to healthy one.…”

“…It was revealed that the expression of psoriasin, a strong E. coli killing AMP, in non-lesional and lesional skin of untreated patients with AD is increased in comparison to healthy controls [46]. Nevertheless, the role of AMPs in the pathogenesis of AD is still unclear.…”