Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity. ROS production was diminished by N-acetylcysteine (NAC) or FX, but not by retinoic acid (RA). In vivo analysis showed that UV irradiation caused sunburn and Flg downregulation, and that FX, but not NAC, RA or clobetasol, exerted a protective effect. FX stimulated Flg promoter activity in a concentration-dependent manner. Flg promoter deletion and chromatin immunoprecipitation analysis showed that caudal type homeo box transcription factor 1 (Cdx1) was a key factor for Flg induction. Cdx1 was also downregulated in UV-exposed skin. Therefore, our data suggested that the protective effects of FX against UV-induced sunburn might be exerted by promotion of skin barrier formation through induction of Flg, unrelated to quenching of ROS or an RA-like action.

Fucoxanthin (FX) is a xanthophyll that is contained abundantly in marine plants. The biological action of FX includes its antioxidant and anti-lipogenic activities, while the precise action of its mechanisms on skin cells has not yet been clarified. The current study examined the effect of FX in comparison with tacrolimus (TAC) on NC/Nga mice, which are an atopic dermatitis (AD) model. FX topical treatment dramatically ameliorated itching behavior over the TAC treatment, which was insufficient for improvement of AD symptoms. In Nc/Nga mice, FX or TAC applied to the skin inhibited eosinophil infiltration with decreased expression of Il-33. FX also stimulated Il-2, Il-5, Il-13, Il-10, and TGF-β expression levels, and Sca1+Il-10+TGF-β+ regulatory innate lymphoid cells (ILCreg) were dominantly observed in FX treated skin epidermal keratinocytes and dermal layers. This combined evidence demonstrated that FX exerts anti-inflammatory effects on keratinocytes and ameliorates AD symptoms by regulating ILCreg to normalize immune responses in an atopic dermatitis model.

Nε-(carboxymethyl) lysine (CML), an advanced glycation end product (AGE), is an aging factor produced by glycation of protein. Higher levels of AGE in skin tissue are related to skin elasticity, but how CML that has accumulated in the skin affects hair follicle formation is unclear. This study constructed a simple model that mimics accumulated glycation from feeding by intradermally injecting Nε-(carboxymethyl) lysine (CML), and examined the effects on the morphogenesis of hair follicles (HF). The results showed weakening of the hair shaft and HF formation by CML. The in vitro inhibitory effect of CML on wound healing of dermal papilla cells (DPC) suggested that the mechanism influences the proliferation and migration of DPC, which are essential for HF morphogenesis. In addition, CML in DPC inhibited the expression of sonic hedgehog (Shh), a factor of tissue morphogenesis, in a NF-kBindependent manner. The findings suggest that the delay in HF formation was due to CML inhibiting proliferation and migration in DPC by inhibiting Shh expression.

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The importance of the transcription factor GATA3 is well established for atopic diseases like allergic asthma bronchiale or atopic dermatitis. Until now, it has almost solely been associated with its function as a master transcription factor for Th2 differentiation and therefore as the responsible factor for the expression of the type 2 cytokines IL-4, IL-13 and IL-5 in T lymphocytes. This function has made GATA3 a promising therapeutic target in Th2 cell based diseases like atopic dermatitis and allergic asthma. We previously reported that fucoxanthin dramatically suppressed GATA1 expression in Nc/Nga mice, indicating that fucoxanthin is a potent inhibitor for itching behavior by modulating mast cell differentiation by regulating GATA1/GATA2 equilibrium. In the current study, we comprehensively documented the effect of fucoxanthin on immunological responses in sebocytes, keratinocytes, macrophage and CD4+ T cells. Fucoxanthin suppressed LPS or Der f1-induced TNF-alfa, IL-6 production in sebocytes, and stimulated phagocytosis by RAW264.7 macrophage cells. Fucoxanthin also inhibited IL-4, IL-5 and IL-13 in CD4+ mouse primary T cells activated by CD3/CD28 T cell activation beads, while CD3+/CD4+/Foxp3+ subsets were increased. These combined evidences demonstrated that fucoxanthin regulates immune-responses by inhibiting GATA3 positive keratinocytes and Th2 helper T cells. Fucoxanthin might be a new therapeutic tool for type I allergy symptoms by regulating GATA3.