Curcumin and visible light as a phytotherapeutic strategy in atopic dermatitis : impact on cytokine-induced inflammation and viral susceptibility in primary human keratinocytes

Abstract

Aim of this thesis was to evaluate the therapeutic efficacy and tolerability of combined curcumin (CUR) and visible light (VIS) treatment in an atopic dermatitis (AD)-relevant primary human keratinocyte (NHK) cell culture model and to establish a translational in vitro system to investigate disease-associated HSV-1 susceptibility, contributing to eczema herpeticum (EH). Combined CUR+VIS suppressed inflammatory signaling while preserving NHK viability within a defined therapeutic window of 0.1–0.2 μg/ml CUR. This was demonstrated by inhibition of TYK2 phosphorylation and reduced IL-8 secretion without cytotoxic effects at 0.2 μg/ml. In contrast, higher concentrations of CUR+VIS induced apoptosis under inflammatory conditions. Neither CUR nor VIS alone significantly affected inflammatory signaling or cell viability, indicating that the observed effects are specific to the combined treatment. HSV-1 susceptibility was assessed in our primary NHK-based in vitro model under varying inflammatory and differentiation conditions. We demonstrate that viral susceptibility was strongly influenced by both the keratinocyte differentiation state and the inflammatory environment. Differentiated NHKs exhibited significantly lower susceptibility than proliferating cells, highlighting the protective role of keratinocyte differentiation. In contrast, an AD-associated cytokine milieu, particularly Th2 cytokines, markedly increased viral susceptibility, whereas interferon-γ exerted antiviral effects across differentiation states. Consistently, an AD-like cytokine profile increased viral susceptibility compared to a psoriasis-like inflammatory environment, demonstrating disease-relevant impairment of keratinocyte antiviral defense consistent with mechanisms underlying EH. Taken together, these findings identify CUR+VIS as a promising anti- inflammatory approach and establish a translational primary keratinocyte-based in vitro model that provides a valuable platform for future investigation of inflammatory signaling and viral susceptibility in AD.