Abstract
Thymus and Activation-Regulated Chemokine (TARC/CCL17) and Macrophage-Derived Chemokine (MDC/CCL22) are two key chemokines exerting their biological effect via binding and activating a common receptor CCR4, expressed at the surface of type 2 helper T (Th2) cells. By recruiting Th2 cells in the dermis, CCL17 and CCL22 promote the development of inflammation in atopic skin. The aim of this research was to develop a plant extract whose biological properties, when applied topically, could be beneficial for people with atopic-prone skin. The strategy which was followed consisted in identifying ligands able to neutralize the biological activity of CCL17 and CCL22. Thus, an in silico molecular modeling and a generic screening assay were developed to screen natural molecules binding and blocking these two chemokines. N-Feruloylserotonin was identified as a neutraligand of CCL22 in these experiments. A cornflower extract containing N-feruloylserotonin was selected for further in vitro tests: the gene expression modulation of inflammation biomarkers induced by CCL17 or CCL22 in the presence or absence of this extract was assessed in the HaCaT keratinocyte cell line. Additionally, the same cornflower extract in another vehicle was evaluated in parallel with N-feruloylserotonin for cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymatic cellular inhibition. The cornflower extract was shown to neutralize the two chemokines in vitro, inhibited COX-2 and 5-LOX, and demonstrated anti-inflammatory activities due mainly to the presence of N-feruloylserotonin. Although these findings would need to be confirmed in an in vivo study, the in vitro studies lay the foundation to explain the benefits of the cornflower extract when applied topically to individuals with atopic-prone skin.
Highlights
Up to 40% of the general population reports to have sensitive skin, and around 9% even have very sensitive skin [1, 2]
CCL17 and CCL22 are key chemokines in atopic dermatitis: the serum levels of these chemokines were found to be elevated in Atopic dermatitis (AD) patients and proportional to disease severity [37, 38]
It was demonstrated that CCR4 played a key role in the induction of acute atopic dermatitis skin lesions in a skin allergic inflammation of BALB/c mice, a strain prone to T-helper 2 (Th2) response [39]
Summary
Up to 40% of the general population reports to have sensitive skin, and around 9% even have very sensitive skin [1, 2]. Sensitive skin encompasses increased skin sensitivity, increased skin irritability, and atopic-prone skin. AD is characterized by infiltration of T-cells, monocytes, and eosinophils in the dermis of lesional skin [4]. Predispositions to these characteristics are observed in atopic-prone skin. One of the predominant physiologic hypotheses regarding atopic skin implies the dysfunction of the natural skin barrier [5]. Environmental factors such as viruses, allergens, or chemicals trigger the secretion of the cytokine thymic stromal lymphopoietin (TSLP) in the keratinocytes, the major cell types of epidermis [6]. After exposure to TSLP, dendritic cells migrate to near lymph nodes to trigger the proliferation of the naive CD4+ T-cells and their subsequent differentiation into type 2 helper
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