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Antioxidant soybean tar G lyteer rescues T ‐helper‐mediated downregulation of filaggrin expression via aryl hydrocarbon receptor
Author(s) -
Takei Kenjiro,
Mitoma Chikage,
HashimotoHachiya Akiko,
Uchi Hiroshi,
Takahara Masakazu,
Tsuji Gaku,
KidoNakahara Makiko,
Nakahara Takeshi,
Furue Masutaka
Publication year - 2015
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.12717
Subject(s) - filaggrin , aryl hydrocarbon receptor , involucrin , downregulation and upregulation , chemistry , loricrin , thymic stromal lymphopoietin , antioxidant , tumor necrosis factor alpha , microbiology and biotechnology , cancer research , keratinocyte , receptor , biochemistry , immunology , biology , atopic dermatitis , transcription factor , in vitro , gene
Soybean tar G lyteer ( G ly) has been widely used for the treatment of various inflammatory skin diseases in J apan since 1924 as an alternative to coal tar remedy. Recently, coal tar has been shown to induce barrier repair in atopic dermatitis via aryl hydrocarbon receptor ( A h R ). In this study, we demonstrated that G ly activated A h R by inducing its cytoplasmic to nuclear translocation in keratinocytes. The A h R ligation by G ly was biologically active, with significant and dose‐dependent upregulation of CYP 1 A 1 expression, which is a specific marker for A h R activation. Gly upregulated the expression of filaggrin in an A h R ‐dependent manner because its enhancing effect was completely abrogated in A h R ‐knockdown keratinocytes. T ‐helper ( T h)2 cytokines inhibited the expression of filaggrin; however, G ly completely restored the T h2‐mediated inhibition of filaggrin expression. Furthermore, G ly coordinately upregulated a series of epidermal differentiation complex genes, including involucrin, loricrin and hornerin. In addition, G ly exhibited potent antioxidant activity through the activation of nuclear factor‐erythroid 2‐related factor‐2 ( N rf2) and downstream antioxidant enzymes such as NAD (P) H :quinone oxidoreductase 1 ( N qo1), which actually inhibited the generation of reactive oxygen species in keratinocytes treated with tumor necrosis factor‐α or benzo[α]pyrene. In conclusion, antioxidant G ly rescues the downregulated expression of filaggrin (and plausibly other barrier proteins) in a T h2‐skewed milieu via A h R activation, which may partly explain its empirical anti‐inflammatory therapeutic effects.