Abstract
The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC’s serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD.
Highlights
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease that affects up to 25% of children and 2–3% of adults [1]
Our findings demonstrated for the first time that serine protease activity is increased in lesions and in non-lesions of AD patients
Our results are consistent with previous reports that the quantity and activity of serine proteases are increased in AD lesions [5,8]
Summary
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease that affects up to 25% of children and 2–3% of adults [1]. Aberrant epidermal serine protease activity is related to the pathogenesis of inflammatory skin diseases such as Netherton syndrome, AD, psoriasis, and rosacea [2,3,4,5,6,7,8]. Transgenic-KLK5 mice display cutaneous and systemic hallmarks of severe inflammation and allergy with pruritus [13]. Transgenic mice expressing human KLK7 in epidermal keratinocytes have been found to develop pathologic skin changes with increased epidermal thickness, hyperkeratosis, dermal inflammation, and severe pruritus [14]. Our group demonstrated that Th2 cytokines increase the KLK7 expression and function in epidermal keratinocytes, suggesting an association between allergic inflammation and epidermal barrier function [15]
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