Galactomyces fermentation filtrate prevents T helper 2‐mediated reduction of filaggrin in an aryl hydrocarbon receptor‐dependent manner

Abstract

SummaryBackground. The aryl hydrocarbon receptor (AhR) recognizes diverse small molecules such as dioxins, tryptophan photoproducts and phytochemicals. It also plays crucial roles in epidermal homeostasis by upregulating epidermal barrier proteins. In preliminary screening, we found that Galactomyces fermentation filtrate (GFF), a cosmetic compound, was capable of activating AhR. Aim. To examine whether GFF upregulates the expression of the filaggrin and loricrin genes, FLG and LOR, in an AhR-dependent manner. Methods. The activation (cytoplasmic to nuclear translocation) of AhR was confirmed by immunofluorescence study and by upregulation of an AhR-specific marker, cytochrome P450-1A1 (CYP1A1). Gene expression levels were compared by quantitative reverse transcription PCR with or without GFF, interleukin (IL)-4 or IL-13 in normal human keratinocytes. AhR or control knockdown was carried out by transfection with AhR or control small interfering RNA. The protein expression of FLG and LOR was examined by immunohistochemistry using a three-dimensional epidermal equivalent treated with or without GFF or T helper (Th)2 cytokines. Results. GFF induced the nuclear translocation of AhR with significant and dosedependent upregulation of CYP1A1, FLG and LOR gene expression. The enhancing effects of GFF were abolished in AhR-knockdown keratinocytes. Th2 cytokines decreased expression of genes for FLG and LOR, and this expression was completely restored in the presence of GFF. The downregulated expression of the FLG gene with its restoration by GFF was also evident in the epidermal equivalent. GFF also upregulated the gene expression of genes encoding occludin, claudin-1 and 4, and kallikrein 5 and 7. Conclusions. Use of GFF is feasible to prevent the Th2-mediated reduction of FLG in an AhR-dependent fashion.

Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

“…It has been increasingly used for cosmetic purposes [57]. Galactomyces fermentation filtrate is also an AHR-stimulant generally used in cosmetics [58]. Interestingly, epigallocatechin gallate and Galactomyces fermentation filtrate exhibit synergistic antioxidant activity against TNFα-induced ROS production (Figure 5).…”

The IL‐13–OVOL1–FLG axis in atopic dermatitis

“…It is intriguing that FLG , OVOL1 and IL13 were the three genes most significantly associated with AD among 31 susceptible gene loci reported in a meta‐analysis of genome‐wide association studies . IL‐4R α signaling by IL‐14 and IL‐13 significantly reduced the expression of FLG, loricrin and involucrin in keratinocytes . At least two mechanisms mediate the IL‐4/IL‐13‐induced FLG down‐regulation: OVOL1 inactivation and the periostin–IL‐24 axis (Fig.…”

“…52 IL-4Ra signaling by IL-14 and IL-13 significantly reduced the expression of FLG, loricrin and involucrin in keratinocytes. 7,[57][58][59][60] At least two mechanisms mediate the IL-4/IL-13-induced FLG down-regulation: OVOL1 inactivation and the periostin-IL-24 axis (Fig. 1).…”

Host-microbiome interactions: the aryl hydrocarbon receptor and the central nervous system

“…Via activation by TCDD, the AHR decreases the permeability of the BBB in vivo [87, 88], but increased BBB permeability was observed following exposure to 3-methylcholanthrene [89]. Interestingly, though the increased BBB permeability reported by Braniste et al has not been assessed in the context of the AHR, a recent study in keratinocytes demonstrated that ligand activation of the AHR elevates occludin and claudin 1 and 4 [90], indicating that a similar AHR-mediated effect could occur in the BBB. One of the most abundant gap junction proteins in the BBB is connexin 43.…”