%0 Journal Article %A Xie, Lixia %A He, Yucheng %A Zhou, Xiaoqiao %A Li, Xiaowen %A Jin, Xiue %A Wang, Xiliang %A Shi, Deshi %D 2018 %T Porcine interleukin-6 enhances the expression of CYP2C33 through a constitutive androstane receptor/retinoid X receptor-mediated pathway %U https://tandf.figshare.com/articles/journal_contribution/Porcine_interleukin-6_enhances_the_expression_of_CYP2C33_through_a_constitutive_androstane_receptor_retinoid_X_receptor-mediated_pathway/5928520 %R 10.6084/m9.figshare.5928520.v1 %2 https://tandf.figshare.com/ndownloader/files/10597264 %K Drug-metabolizing enzymes %K CYP2C33 %K hepatocytes %K interleukin-6 %K constitutive androstane receptor %X

Cytochrome P450, which is expressed in humans and other animals, is a superfamily of drug-metabolizing enzymes that play important roles in the metabolism of endogenous and xenobiotic substrates via oxidation, peroxidation and reduction. Of endogenous substrates, interleukin (IL)-6 is a crucial cytokine involved in inflammation in the liver. The present study aims to elucidate the mechanisms through which IL-6 modulates cytochrome P450 expression.

CYP2C33 expression was found to be increased in HepLi cells and primary porcine hepatocytes treated with IL-6 in a concentration-dependent manner. IL-6 treatment also increased the expression of the transcriptional regulators, constitutive androstane receptor (CAR) and pregnane X receptor.

Overexpression of CAR promoted CYP2C33 expression at the mRNA and protein levels, whereas knockdown of CAR by small interfering RNA reduced CYP2C33 expression. Luciferase assays showed that IL-6 treatment of HepLi cells and primary porcine hepatocytes increased CYP2C33 promoter activity. Co-immunoprecipitation and western blotting demonstrated that CAR and RXR could form heterodimers.

IL-6 affects CYP2C33 expression through CAR/retinoid X receptor (RXR) heterodimers.

Cytochrome P450, which is expressed in humans and other animals, is a superfamily of drug-metabolizing enzymes that play important roles in the metabolism of endogenous and xenobiotic substrates via oxidation, peroxidation and reduction. Of endogenous substrates, interleukin (IL)-6 is a crucial cytokine involved in inflammation in the liver. The present study aims to elucidate the mechanisms through which IL-6 modulates cytochrome P450 expression.

CYP2C33 expression was found to be increased in HepLi cells and primary porcine hepatocytes treated with IL-6 in a concentration-dependent manner. IL-6 treatment also increased the expression of the transcriptional regulators, constitutive androstane receptor (CAR) and pregnane X receptor.

Overexpression of CAR promoted CYP2C33 expression at the mRNA and protein levels, whereas knockdown of CAR by small interfering RNA reduced CYP2C33 expression. Luciferase assays showed that IL-6 treatment of HepLi cells and primary porcine hepatocytes increased CYP2C33 promoter activity. Co-immunoprecipitation and western blotting demonstrated that CAR and RXR could form heterodimers.

IL-6 affects CYP2C33 expression through CAR/retinoid X receptor (RXR) heterodimers.

%I Taylor & Francis