Journal: Archives of toxicology

Article Title: The Toll-like receptor agonist imiquimod is metabolized by aryl hydrocarbon receptor-regulated cytochrome P450 enzymes in human keratinocytes and mouse liver

doi: 10.1007/s00204-019-02488-5

Figure Lengend Snippet: (a) Microsomal preparations of 21 heterologously expressed human CYP isoforms were incubated with 0.5 μM IMQ for 15 min at 37°C. IMQ content was determined by LC/MS. (ins. Ctrl = control insect cell preparation; n = 2). (b) Formation of monohydroxylated IMQ metabolites (RT = retention time) by four of the 21 heterologously expressed human CYP isoforms. (c) HaCaT keratinocytes were pre-treated for 24 hrs with 0.5 μM BaP or solvent. Next, cells were treated with 0.5 μM IMQ alone and in combination with 5 μM 7-HF and 2 μM furafylline (Fura). After 6 hrs, monohydroxylated IMQ metabolites in the cell culture supernatants were determined by LC/MS (n = 3). (d) HaCaT keratinocytes were pre-treated for 24 hrs with 0.5 μM BaP or solvent. Subseqeuntly, cells were treated with 1 μM granisetron alone and in combination with 5 μM 7-HF, 2 μM furafylline (Fura) and 0.5 μM IMQ. The amount of 7-hydroxylated granisetron in the cell culture supernatants was assessed after 6 hrs by LC/MS (n ≥ 4). (n.d. = not detectable; n.s. = not significant; * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.005).

Article Snippet: Furafylline was obtained from Cayman Chemicals (Ann Arbor, MI, USA) and 7-ethoxyresorufin from Santa Cruz Biotechnology (Heidelberg, Germany).

Techniques: Incubation, Liquid Chromatography with Mass Spectroscopy, Control, Solvent, Cell Culture