Galactomyces fermentation filtrate prevents T helper 2‐mediated reduction of filaggrin in an aryl hydrocarbon receptor‐dependent manner
Open accessAbstract
Background 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 dose-dependent 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 ex…
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GFF activates aryl hydrocarbon receptor and enhances the expression of filaggrin, which is an essential source of natural moisturizing factors.
“GFF is known to activate aryl hydrocarbon receptor and enhance the expression of filaggrin, which is an essential source of natural moisturizing factors [5,9].”
GFF works as a potent antioxidative agonist for aryl hydrocarbon receptor.
“SK-II Pitera™ contains Galactomyces ferment filtrate (GFF), which works as a potent antioxidative agonist for aryl hydrocarbon receptor [5,6].”
GFF increases the expression of filaggrin, caspase-14, and claudin-1, which may facilitate the production of natural moisturizing factors and strengthen the tight junction structure.
“GFF is known to increase the expression of filaggrin, caspase-14, and claudin-1, which may facilitate the production of natural moisturizing factors and strengthen the tight junction structure [5,7,8].”
GFF activates the aryl hydrocarbon receptor (AHR).
“Recent studies have demonstrated that GFF activates an aryl hydrocarbon receptor (AHR)”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
GFF operates as a potent antioxidative AHR agonist.
“it has been demonstrated to operate as a potent antioxidative AHR agonist [10,55,56].”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
GFF increases the expression of claudin-1, claudin-4, occludin, and ZO-1 in keratinocytes.
“Notably, GFF increases the expression of claudin-1, claudin-4, occludin, and ZO-1 in keratinocytes [55,81,100] (Figure 2).”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
AHR knockdown partially downregulates occludin expression but does not affect claudin-1 or claudin-4 expression.
“The knockdown of AHR partially downregulates the expression of occludin, whereas it does not affect the expression of claudin-1 or claudin-4 [55].”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
GFF upregulates the expression of filaggrin in epidermal keratinocytes.
“upregulates the expression of filaggrin, a pivotal endogenous source of natural moisturizing factors, in epidermal keratinocytes.”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
GFF counteracts the IL-4- and IL-13-mediated downregulation of filaggrin expression.
“Notably, GFF is capable of counteracting the IL-4- and IL-13-mediated downregulation of filaggrin expression [55].”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
GFF counteracts the IL-4-induced inhibition of loricrin expression.
“In addition to the upregulation of filaggrin, GFF upregulates the expression of loricrin and counteracts the IL-4-induced inhibition of loricrin expression [55].”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
Upon GFF stimulation, activated AHR translocates from the cytoplasm into the nucleus in keratinocytes.
“Upon stimulation by GFF, activated AHR translocates into the nucleus from the cytoplasm (Figure 1), where it upregulates the expression of filaggrin [55].”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
The GFF-mediated upregulation of claudin-1 and claudin-4 is independent of AHR activation.
“These results indicate that the GFF-mediated upregulation of claudin-1 and claudin-4 is independent of AHR activation.”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
GFF-mediated filaggrin upregulation is AHR-dependent, as it is abrogated by AHR knockdown.
“GFF-mediated filaggrin upregulation is AHR-dependent because it is abrogated by the knockdown of AHR [55] (Figure 2).”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
GFF upregulates the expression of loricrin.
“In addition to the upregulation of filaggrin, GFF upregulates the expression of loricrin and counteracts the IL-4-induced inhibition of loricrin expression [55].”
From Galactomyces Ferment Filtrate Potentiates an Anti-Inflammaging System in Keratinocytes (2022) · cites this paper as [55]
AHR-targeting antioxidant phytochemicals or antioxidant medicinal chemicals do not generate appreciable amounts of reactive oxygen species, probably due to efficient induction of antioxidant enzymes mediated by NRF2 activation.
“Notably, the AHR-targeting antioxidant phytochemicals or antioxidant medicinal chemicals do not generate appreciable amounts of reactive oxygen species probably due to efficient induction of antioxidant enzymes mediated by NRF2 activation [19,20,21,27].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [27]
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- Authors
- Takei, K., Mitoma, C., Hashimoto‐Hachiya, A., Takahara, M., Tsuji, G., Nakahara, T., & Furue, M.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Furue, M.
- Venue
- Clinical and Experimental Dermatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-03-18
- Volume
- 40
- Issue
- 7
- Pages
- 786-793
- ISSN
- 0307-6938 (ISSN-L)
- 1365-2230
- OpenAlex
- W2068915983
- Cited by
- 45
- References
- 21
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical and Experimental Dermatology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- P&G Innovation Godo Kaisha
- Ministry of Health, Labour and Welfare
- Environment Technology Development Fund of the Ministry of the Environment, Japan
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- aryl hydrocarbon receptor, filaggrin, loricrin, Th2 cytokines, IL-4, IL-13, skin barrier, keratinocytes, CYP1A1, occludin, claudins, kallikrein, epidermal equivalents
- MeSH terms
- Epidermal Cells, Filaggrin Proteins, Analysis of Variance, Cells, Cultured, Saccharomycetales, Fermentation, T-Lymphocytes, Helper-Inducer, Humans, Intermediate Filament Proteins, Membrane Proteins, Transfection, Keratinocytes, Up-Regulation, Receptors, Aryl Hydrocarbon, Microscopy, Confocal, Cytochrome P-450 CYP1A1, Reverse Transcriptase Polymerase Chain Reaction
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