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. 2014 Feb;134(2):556-559.
doi: 10.1038/jid.2013.362. Epub 2013 Aug 30.

The new aryl hydrocarbon receptor antagonist E/Z-2-benzylindene-5,6-dimethoxy-3,3-dimethylindan-1-one protects against UVB-induced signal transduction

Julia Tigges  1 , Thomas Haarmann-Stemmann  1 , Christoph F A Vogel  2 , Annemarie Grindel  2 , Ulrike Hübenthal  1 , Heidi Brenden  1 , Susanne Grether-Beck  1 , Gabriele Vielhaber  3 , William Johncock  3 , Jean Krutmann  4 , Ellen Fritsche  1
Affiliations

The new aryl hydrocarbon receptor antagonist E/Z-2-benzylindene-5,6-dimethoxy-3,3-dimethylindan-1-one protects against UVB-induced signal transduction

Julia Tigges et al. J Invest Dermatol. 2014 Feb.
No abstract available

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Conflict of interest statement

CONFLICT OF INTEREST

JK serves as scientific consultant for Symrise GmbH & Co. KG, Holzminden, Germany.

Figures

Figure 1
Figure 1. Characterization of antagonistic capacities of E/Z-2-benzylidene-5,6-dimethoxy-3,3-dimethylindan-1-one (BDDI) in normal human epidermal keratinocytes (NHEKs)
(a) Chemical structure of BDDI. (b) Effect of BDDI on cell viability (CellTiter Blue; CTB) and cytotoxicity (lactate dehydrogenase; LDH). The black line marks the respective control level. (c) Effect of BDDI on B(a)P (250 nM for 4 hours)-, 6-formylindolo[3,2-b]carbazole (FICZ; 100 nM for 4 hours)-, and UVB (100 Jm−2 for 8 hours)-induced CYP1A1 mRNA expression (quantitative reverse transcription-PCR data). (d) Effect of BDDI on 7-O-ethoxyresorufin-deethylase (EROD) activity induced by 24 hours B(a)P shown in activity as pmol min−1−mg−1. (e) Transient effect of BDDI pretreatment (1 and 24 hours) on CYP1A1 mRNA expression induced by 100 Jm−2 UVB. (f) NHEKs were irradiated with 100 Jm−2 UVB and directly after irradiation treated with 3.3 and 33 µM BDDI. After 8 hours, RNA was isolated, and CYP1A1 transcription was analyzed. Each graph represents mean±SEM of three independent experiments; *P<0.05 versus medium/DMSO control; #P<0.05 versus treatment (B(a)P, FICZ, or UVB, respectively).
Figure 2
Figure 2. BDDI disturbs XRE binding of aryl hydrocarbon receptor (AhR)/ARNT and represses UVB-induced gene expression in a human in vivo study
(a) HaCaT keratinocytes were treated with 10 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 100 nM 6-formylindolo[3,2-b]carbazole (FICZ), 10 µM 3′-methoxy-4′-nitroflavone (MNF), and/or 3.3 µM BDDI for 90 minutes before isolation of nuclear extracts and were hybridized with a xenobiotic-responsive element (XRE) consensus oligonucleotide. A representative electrophoretic mobility shift assay of three independent experiments is shown. (b) Volunteers were pretreated with 0.5% BDDI or placebo for 4 days every day followed by UVB irradiation (1.5 minimal erythema dose, MED) on day 4. Twenty-four hours after irradiation, 4-mm skin biopsies were taken, RNA was isolated and reverse transcribed, and mRNA expression of CYP1A1, cyclooxygenase-2, and matrix metalloproteinase-1 was measured. Gene expression in sham-irradiated, untreated control skin were arbitrarily set as 1; n=10, mean±SEM, *P<0.001 versus unirradiated control, #P<0.001 versus UVB (1.5 MED).
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References

    1. Abel J, Haarmann-Stemmann T. An introduction to the molecular basics of aryl hydrocarbon receptor biology. Biol Chem. 2010;391:1235–1248. - PubMed
    1. Agostinis P, Garmyn M, Van Laethem A. The aryl hydrocarbon receptor: an illuminating effector of the UVB response. Sci STKE. 2007;2007:e49. - PubMed
    1. Denison MS, Fisher JM, Whitlock JP., Jr The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis. J Biol Chem. 1988;263:17221–17224. - PubMed
    1. Elmets CA, Viner JL, Pentland AP, et al. Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, doubleblind, placebo-controlled trial. J Natl Cancer Institute. 2010;102:1835–1844. - PMC - PubMed
    1. Fritsche E, Schafer C, Calles C, et al. Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation. Proc Natl Acad Sci USA. 2007;104:8851–8856. - PMC - PubMed

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