AhR is required for skatole-mediated CYP1A1 and CYP1A2 up-regulation.

<p>(A) RT-qPCR analysis of <i>AhR</i>, <i>CYP1A1</i> and <i>CYP1A2</i> mRNA expression in PHHs (Donor #391) after siRNA-mediated <i>AhR</i> down-regulation. (B) RT-qPCR analysis of <i>CYP1A1</i> (B) and <i>CYP1A2</i>(C) mRNA expression in PHHs after siRNA-mediated <i>AhR</i> down-regulation and incubation with 50 or 100 μM skatole, or 10 nM TCDD. * significantly different from cells transfected with non-target siRNA.</p

Skatole increases CYP1A1 expression in HepG2-C3 cells and PHHs.

<p>RT-qPCR analysis of <i>CYP1A1</i> (A) and <i>AhR</i> (B) mRNA expression following incubation of HepG2-C3 cells with 1, 10 or 100 μM skatole for 2, 4, 8 or 24 h (n = 3). (C) CYP1A and actin protein expression in PHHs (Donor #400) after incubation with 10, 50 or 100 μM for 24 h. * Significantly different from time-matched control cells (no treatment) (Student’s t–test; p < 0.001).</p

<i>CYP1A1</i>, <i>CYP1A2</i>, <i>CYP1B</i>1 and <i>AhR</i> mRNA expression in PHHs (n = 5) incubated with 1, 10, 100 μM skatole or 10 nM TCDD for 8 or 24 hours.

<p><i>CYP1A1</i>, <i>CYP1A2</i>, <i>CYP1B</i>1 and <i>AhR</i> mRNA expression in PHHs (n = 5) incubated with 1, 10, 100 μM skatole or 10 nM TCDD for 8 or 24 hours.</p

Clinical characteristics of the liver donors.

<p>Clinical characteristics of the liver donors.</p

Schematic model of the impact of skatole on AhR activity, as suggested from the findings of this work.

<p>Schematic model of the impact of skatole on AhR activity, as suggested from the findings of this work.</p

Primer sequences.

<p>Primer sequences.</p

Indole-3-carbinol (I3C) induces CYP1A1 expression and activates AhR.

<p>(A) RT-qPCR analysis of <i>CYP1A1</i> mRNA expression in HepG2-C3 cells incubated with 0.1, 1 or 10 μM I3C for 24 h (n = 3). (B) Relative luciferase activity measured in HAhLH or HepAhLH cells incubated with I3C (from 1.10−⁷ M to 1.10−⁴ M) for 8 h (n = 3). (C) RT-qPCR analysis of <i>CYP1A1</i> mRNA expression in HepG2-C3 cells incubated with 10 nM TCDD alone or in the presence of 0.1, 1 or 10 μM I3C (n = 3). Bars not sharing subscription are significantly different (p < 0.05).</p