Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker gene ID2, by contact sensitizers in human bulge-derived keratinocytes.
In the epidermis, keratinocytes are involved in physical and first-line immune protection of the host. In this study, we analyzed the molecular responses to certain contact sensitizers (2,4-dinitrochlorobenzene and NiSO(4)) and irritants (sodium dodecyl sulfate and benzalkonium chloride) in cultured human keratinocytes from the bulge region of a plucked hair follicle (bulge-derived keratinocytes [BDKs]) and compared these molecular responses to those with the human monocytic leukemia cell line, THP-1. The BDKs, individually established without invasive biopsies, showed high reactivity to these stimulants. As a primary response to the contact sensitizers, the NRF2-mediated signaling pathway was upregulated in BDKs and THP-1. The expression of IL1B and IL8 genes was not induced by the irritants but by the sensitizers in THP-1. However, the expression of the IL1B and IL8 genes was induced at higher levels by the irritants in BDKs than by the sensitizers. Many genes orchestrating keratinocyte differentiation, including ID2, were significantly upregulated in response to the sensitizers in BDKs but not those in THP-1. The use of the ID2 gene to discriminate between sensitizers and irritants might be effective as a novel marker for application during in vitro sensitization with BDKs.
Department of Genetics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. yoshiey@hyo-med.ac.jp
Yoshie
Y
Yoshikawa
Yusuke
Y
Sasahara
Yukio
Y
Kitano
Nozomi
N
Kanazawa
Hiroki
H
Shima
Tomoko
T
Hashimoto-Tamaoki
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000378:metabolism; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000166:cytology*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007509:Irritants / Q000633:toxicity*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
D015415:Biomarkers; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D007378:Interleukins; D007509:Irritants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human