TY - JOUR
T1 - An acid-hydrolyzed wheat protein activates the inflammatorand nf-κb pathways leading to long tslp transcription in human keratinocytes
AU - Kuroda, Yasutaka
AU - Yuki, Takuo
AU - Takahashi, Yutaka
AU - Sakaguchi, Hitoshi
AU - Matsunaga, Kayoko
AU - Itagaki, Hiroshi
N1 - Publisher Copyright:
© 2020, Japanese Society of Toxicology. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Hydrolyzed wheat proteins (HWPs) contained in cosmetics have occasionally caused immediate-type hypersensitivity following repeated skin exposure. Although the Cosmetic Ingredient Review Expert Panel concluded that < 3,500 Da HWP is safe for use in cosmetics, it remains biological-ly unknown how allergenic HWPs evoke immediate-type allergy percutaneously. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) induces type 2 immune responses, which play an essential role in the pathogenesis of immediate-type allergy. Previously, we demonstrated that protein allergens in cultured human keratinocytes strongly induced long-form TSLP (loTSLP) transcription. However loTSLP-regulat-ing signaling by HWP is poorly understood. In this study, we performed global gene expression analysis by microarray to investigate how the allergenic HWP acts on epidermal keratinocytes and the induction of loTSLP. Compared to human serum albumin (HSA), allergenic HWP induced a distinct gene expression pattern and preferentially activated various inflammatory pathways (High Mobility Group Box 1, Interleukin [IL]-6, IL-8, and acute phase response signaling). We identified 85 genes as potential nuclear fac-tor-kappa B (NF-κB) target genes in GP19S-treated cells, compared with 29 such genes in HSA-treat-ed cells. In addition, HWP specifically altered IL-17 signaling pathways in which transcription factors, NF-κB and activator protein-1, were activated. NF-κB signaling may be an important factor for HWP-induced inflammatory loTSLP transcription via inhibition assay. In conclusion, allergenic HWP caused an easily sensitizable milieu of activated inflammatory pathways and induced NF-κB-dependent loTSLP transcription in keratinocytes.
AB - Hydrolyzed wheat proteins (HWPs) contained in cosmetics have occasionally caused immediate-type hypersensitivity following repeated skin exposure. Although the Cosmetic Ingredient Review Expert Panel concluded that < 3,500 Da HWP is safe for use in cosmetics, it remains biological-ly unknown how allergenic HWPs evoke immediate-type allergy percutaneously. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) induces type 2 immune responses, which play an essential role in the pathogenesis of immediate-type allergy. Previously, we demonstrated that protein allergens in cultured human keratinocytes strongly induced long-form TSLP (loTSLP) transcription. However loTSLP-regulat-ing signaling by HWP is poorly understood. In this study, we performed global gene expression analysis by microarray to investigate how the allergenic HWP acts on epidermal keratinocytes and the induction of loTSLP. Compared to human serum albumin (HSA), allergenic HWP induced a distinct gene expression pattern and preferentially activated various inflammatory pathways (High Mobility Group Box 1, Interleukin [IL]-6, IL-8, and acute phase response signaling). We identified 85 genes as potential nuclear fac-tor-kappa B (NF-κB) target genes in GP19S-treated cells, compared with 29 such genes in HSA-treat-ed cells. In addition, HWP specifically altered IL-17 signaling pathways in which transcription factors, NF-κB and activator protein-1, were activated. NF-κB signaling may be an important factor for HWP-induced inflammatory loTSLP transcription via inhibition assay. In conclusion, allergenic HWP caused an easily sensitizable milieu of activated inflammatory pathways and induced NF-κB-dependent loTSLP transcription in keratinocytes.
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U2 - 10.2131/jts.45.327
DO - 10.2131/jts.45.327
M3 - Article
C2 - 32493875
AN - SCOPUS:85086008630
SN - 0388-1350
VL - 45
SP - 327
EP - 337
JO - Journal of Toxicological Sciences
JF - Journal of Toxicological Sciences
IS - 6
ER -