Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease that can cause skin barrier function damage. Although co-incubation with docosahexaenoic acid (DHA) exerts a positive effect on deficient skin models, no studies have investigated the effects of topical treatment with DHA in an inflammatory reconstructed human epidermis (RHE) model. The effects of DHA on monolayer normal human epidermal keratinocyte (NHEK) cells were evaluated using cell counting kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The skin-related barrier function was assessed using hematoxylin–eosin (HE) staining, Western blot (WB), immunohistofluorescence (IF), and ELISA in normal and inflammatory RHE models. Docosahexaenoic acid upregulated filaggrin and loricrin expression at mRNA levels in addition to suppressing overexpression of tumor necrosis factor-α (TNF-α), interleukin-α (IL-1α), and interleukin-6 (IL-6) stimulated by polyinosinic–polycytidylic acid (poly I:C) plus lipopolysaccharide (LPS) (stimulation cocktail) in cultured NHEK cells. After topical treatment with DHA, cocktail-induced inflammatory characteristics of skin diseases, including barrier morphology, differentiation proteins, and thymic stromal lymphopoietin (TSLP) secretion, were alleviated in RHE models. Supplementation with DHA can improve related barrier function and have anti-inflammation effects in monolayer keratinocytes and RHE models, which indicates that DHA may have potential value for the treatment of inflammation-associated skin diseases.
Highlights
The skin barrier, consisting of dermis and upper epidermis, is the first physical protective barrier of the human body
Profilaggrin generates filaggrin monomers that can aggregate and link keratin to form a cornified envelope (CE), which has a critical role in maintaining the integrity of the stratum corneum (SC) [3]
Filaggrin is a core epidermal protein that plays an important role for its intracellular metabolites that make contributions to epidermal barrier functions such as SC hydration and inhibition of UV-B irradiation [4]
Summary
The skin barrier, consisting of dermis and upper epidermis, is the first physical protective barrier of the human body. The epidermis, a multi-layered compartment, protects humans from negative external environmental factors by preventing foreign pathogens, reducing water loss, and maintaining the homeostasis of skin through cell death and differentiation of keratinocyte [1,2]. Filaggrin is a core epidermal protein that plays an important role for its intracellular metabolites that make contributions to epidermal barrier functions such as SC hydration and inhibition of UV-B irradiation [4]. Molecules 2019, 24, 3156; doi:10.3390/molecules24173156 www.mdpi.com/journal/molecules core epidermal protein that plays an important role for its intracellular metabolites that make contributions to epidermal barrier functions such as SC hydration and inhibition of UV-B irradiation [4]
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