Anti-KLK5 monoclonal antibody, clone NN0543-5E38

There is mounting evidence that Th2 cytokines adversely affect skin barrier functions and contribute to the pathogenesis of atopic dermatitis (AD). AD is also characterized by abnormal cohesion in the stratum corneum (SC). However, the contribution of Th2 cytokines to this abnormality remains unknown. This study examined the effects of IL-4, a prototypic Th2 cytokine, on the cohesion of the SC. Structural and physiological assessments revealed that repeated intradermal injections of IL-4 compromised the cohesion of the SC of normal hairless mice. Two potential mechanisms were explored to account for the altered cohesion. First, IL-4 decreased the amount of corneodesmosomes and down-regulated the expression of desmoglein 1, but not of corneodesmosin (CDSN) or loricrin expression, in murine skin and in cultured human keratinocytes (KC). IL-4 did not affect the skin surface pH, and in situ zymography revealed no net change in total serine protease activity in the IL-4-treated SC. Yet, IL-4 enhanced expression of kallikrein (KLK)7, while simultaneously down-regulating KLK5 and KLK14. Finally, IL-4 did not alter the expression of the lympho-epithelial Kazal-type inhibitor (LEKTI) in KC. This study suggests that IL-4 abrogates the cohesion of SC primarily by reducing epidermal differentiation.

The stratum comeum tryptic enzyme kallikrein 5 (KLK5) is a serine protease that is involved in the cell renewal and maintenance of the skin barrier functions. The excessive activation of KLK5 causes an exacerbation of dermatoses, such as rosacea and atopic dermatitis. Nasturtium officinale R. Br. (Brassicaceae) is a hardy perennial plant native to Europe and commonly called "Watercress" or "Cresson," which is one of the brassica vegetables. We aimed to investigate whether the bioactive sulfur-containing compound inhibits the KLK5 protease. The sulfur-containing compounds were evaluated using an enzymatic assay to measure the anti-KLK5 activity. Our study revealed that the sulfur-containing compound inhibits the KLK5 and 7 protease activity. Indole-3-acetonitrile-4-methoxy-2-S-beta-D-glucopyranoside may affect the skin barrier and atopic function via the regulation of proteases.