title: Induction of AhR-mediated gene transcription by coffee.
abstract: BACKGROUND
  Aryl hydrocarbon receptor (AhR) is classically known to be activated by xenobiotics such as dioxins and polycyclic aromatic hydrocarbons (PAHs). Although it has been reported that PAHs are contained in roasted coffee beans, in general coffee beverages are not considered to be AhR activators. We tested whether exposure to coffee would activate AhR in cultured cells.
  
  
  METHODS
  HepG2 cells stably expressing an AhR-responsive reporter gene were treated with coffee samples. Also, expression of CYP1A1, an endogenous AhR-responsive gene, was quantitated by RT-PCR and Western blotting in HepG2, Caco-2, and MCF-7 cells, after treatment with coffee. In order to obtain sensitive and reproducible results, all the experiments were performed with the cells placed in either phosphate-buffered saline (PBS) or pure serum, instead of routinely-used culture medium, whose intrinsic AhR-stimulating activity turned out to be so strong as to interfere with the analyses.
  
  
  RESULTS
  All the coffee samples tested robustly stimulated AhR-mediated transcription in the reporter gene assays. Of note, to what extent coffee and other AhR agonists activated AhR was different, depending on whether the experiments were done in PBS or serum. CYP1A1 mRNA was induced by coffee, in HepG2, Caco-2, and MCF-7 cells placed in either PBS or serum. CYP1A1 protein expression, which was not detected in these cells incubated in PBS, was also increased by coffee in cells placed in serum.
  
  
  CONCLUSIONS
  By using culture medium-free experimental settings, we have shown that coffee is a strong AhR activator. Our observation may help elucidate as-yet-unrecognized effects of coffee on human health.
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okinaga
authors.affiliation: Teikyo Academic Research Center, Teikyo University, Tokyo, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Teramoto
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D018938:Caco-2 Cells; D003069:Coffee / Q000737:chemistry* / Q000145:classification; D003470:Culture Media / Q000737:chemistry; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003069:Coffee; D003470:Culture Media; D019363:Cytochrome P-450 CYP1A1; D010936:Plant Extracts; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C569463:CYP1A1 protein, human