The aryl hydrocarbon receptor (AHR) is a transcription factor that regulates gene expressions in response to endogenous and exogenous signals. FICZ is a high potency AHR agonist with a Kd value of 0.07 nM[3]. The 24-h treatment with 100 nM FICZ significantly induced EROD activity in wild-type mouse hepatoma Hepa-1 cells. FICZ at the concentration of 1 nM increased the mRNA level of CYP1A1 in wild-type cells, but the induction was transient and declined 3h after the treatment. In c37 cells, FICA-induced CYP1A1 mRNA expression was sustained[4]. In human liver microsomes, a 20-min preincubation with a mixture of CYP1A1/1A2 and CYP1B1 antibodies almost completely blocked (93%) the NADPH-dependent FICZ metabolism. In HepG2 cells treated with 5 nM FICZ, the addition of 5 μM αNF attenuated the complete depletion of intracellular levels of FICZ as compared to non-αNF treated cells. CYP1A1 catalyzes the hydroxylation of FICZ with extremely high efficiency (Kcat/Km = 8.1 × 107M-1s-1[5]. In a mouse model of mite-induced chronic dermatitis, treatment with FICZ ointment at the dose of 10-3 mM for 2 weeks significantly improved the dermatitis compared to control mice[6].
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