990 0.005% hypochlorite reduces serine protease in cultured human keratinocytes and alleviates itch of atopic skin

Abstract

Proper serine protease (SP) regulation is essential for the homeostasis of epidermal permeability barrier. The imbalance between the activities of SPs and SP inhibitors contributes to disease flares in atopic dermatitis (AD). Bleach bath (0.005% hypochlorite (HOCl) has been included in the armamentarium for treating AD, but the mechanism involved in this treatment strategy remains unclear. This study aimed to determine the direct effect of 0.005% HOCl on cultured human keratinocytes in terms of SP expressions and to document the clinical effects of bleach bath on atopic skin. Stimulated cultured human keratinocytes were pretreated with 0.005% HOCl, and alterations in SP and SP inhibitor expressions as well as SP activities were evaluated. The potential involved molecular pathway was investigated. Additionally, the itch scores and skin physiologic profiles were documented before and within one day after bleach bath in patients with moderate to severe AD. Our results showed that the expression of SP kallikrein-related peptidase 5 (KLK5) and KLK7 in cultured keratinocytes were significantly upregulated by IL-1β. Pretreatment with 0.005% HOCl abrogated this phenomenon. Attenuation of nuclear factor kappa B (NFκB) signaling was found to involve in this process. The itch scores and skin pH were remarkably reduced within one day after bleach bath in AD patients while no significant change was noted in terms of stratum corneum hydration and epidermal water loss profiles. In summary, 0.005% HOCl has direct impact on cultured human keratinocytes in terms of SP expression and activity via modulation of NFκB pathway. As SP plays an important role maintaining epidermal integrity and modulating itching sensation, the direct effects of HOCl on epidermal keratinocytes contributed to the favorable therapeutic effect of bleach bath on atopic skin.