Treatment with Docosahexaenoic Acid Improves Epidermal Keratinocyte Differentiation and Ameliorates Inflammation in Human Keratinocytes and Reconstructed Human Epidermis Models

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.

Diet and Skin Barrier: The Role of Dietary Interventions on Skin Barrier Function

“…Studies in skin models and cultured human keratinocytes suggest that DHA can increase filaggrin expression, attenuate inflammation, and improve epidermal keratinocyte differentiation [36][37][38]. An animal study demonstrated decreased TEWL, increased skin hydration, and decreased skin barrier alteration by acetone [39].…”

“…EPA and the ester of EPA have been shown in animal studies to influence ceramides in skin [40,41]. However, studies have utilized different methodologies and have shown varying improvement [36][37][38].…”

Retaining Skin Barrier Function Properties of the Stratum Corneum with Components of the Natural Moisturizing Factor—A Randomized, Placebo-Controlled Double-Blind In Vivo Study

“…The lateral lipid organization, which is responsible for SC permeation and the water binding properties of NMF represent the two major factors in providing skin hydration [ 27 , 33 ]. Among other cosmetic substances [ 34 , 35 , 36 ], the topical application of an NMF containing substance is an important factor for improvement of the skin barrier function.…”

New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression

“…All tested topical PPAR-β/δ agonists (GW1514), PPAR-α agonists (clofibrate, and WY-14,643), and PPAR-γ agonists (ciglitazone and troglitazone) stimulate FLG production and keratinocyte differentiation and improve multiple parameters of the AD-like dermatosis in vitro and in mice models [ 193 , 194 , 195 ]. More recently, docosahexaenoic acid (DHA), a dual PPARα/γ agonist was shown to increase the expression of FLG and have anti-inflammation effects in monolayer keratinocytes and reconstructed human epidermis models [ 196 ]. Czarnowicki et al reported also promising results for the liver X receptor (LXR) agonist.…”