DUOX expression in human keratinocytes and bronchial epithelial cells: Influence of vanadate

• Published in: Toxicology in vitro 2018-02, Vol.46, p.257-264
• Main Authors: Hill, Thomas, Rice, Robert H.
• Format: Article
• Language: English
• Subjects: Animal tissues; Arsenite; Bronchi - cytology; Cadmium; Cell Line; Cells; Chromate; Chromates; Copper compounds; Cytokines; Dual Oxidases - genetics; Dual Oxidases - metabolism; DUOX; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Human bronchial cells; Human epidermal keratinocytes; Humans; Interferon; Interferon γ; Interleukin 4; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Lead; Metalloid compounds; Metals; mRNA; Mucosa; Oxygen; Stibnite; Stimulation; Studies; Vanadate; Vanadates; Vanadates - pharmacology; γ-Interferon
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2017.10.010

Dual oxygenases (DUOX) 1 and 2, expressed in many animal tissues, participate in host defense at mucosal surfaces and may have important signaling roles through generation of reactive oxygen. Present work addresses their expression in cultured human epidermal keratinocytes and effects of cytokines and metal/metalloid compounds. Both DUOX1 and 2 were expressed at much higher levels after confluence than in the preconfluent state. Maximal DUOX1 mRNA levels were 50 fold those of DUOX2. DUOX1 and 2 were induced ≈3 fold by interleukin 4, but only DUOX1 was induced by interferon gamma (IFNγ). In human bronchial HBE1 cells, by contrast, interleukin 4 induced only DUOX 1, and IFNγ induced only DUOX2. A survey in the keratinocytes of metal/metalloid compounds showed that arsenite, antimonite, chromate, cadmium, copper, lead and vanadate suppressed DUOX1 levels but did not prevent interleukin 4 stimulation. Effects on DUOX2 were less dramatic, except that vanadate potentiated the stimulation by IFNγ up to 7 fold. The results indicate that epithelial cell types of different tissue origins can differ in their cytokine regulation and that epidermal cells can exhibit striking alterations in response due to certain metal/metalloid exposures. •Baseline DUOX expression in epidermal keratinocytes was maximal after confluence.•DUOX1 and 2 were stimulated by IL4, but only DUOX2 by IFNγ in epidermal keratinocytes.•In bronchial epithelial cells, IL4 induced DUOX1, while IFNγ induced DUOX2.•Vanadate markedly increased DUOX2 induction by IFNγ in epidermal keratinocytes.