Fig. 4.

IL-1β-induced NF-κB signaling suppresses FXR and ABCB11. a Liver mRNA for Nr1h4 in WT, Ccr2^−/−, or Il1r^−/− DSS/chow and DSS/PN mice. *p < 0.05 vs. all other groups. One-way ANOVA and Tukey's correction. b Relative mRNA expression of Nr1h4 in the liver of untreated and IL-1β- exposed (i.p. for 4 h) mice and in HuH7 cells and primary mouse hepatocytes left untreated or exposed to IL-1β for 4 h (depicting mean ± SEM of technical triplicates from one representative out of at least five experiments). *p < 0.05 IL-1β vs. untreated by t test. c, d Liver mRNA for Nr1h4 in untreated and LPS-exposed (2.5 mg/kg i.p. for 4 h) mice with and without prior i.p. treatment (16 h) with clodronate-liposomes (Clo-lip) and c relative to untreated and LPS exposed WT, Casp1/11^−/−, or Il1r^−/− mice. *p < 0.05 vs. untreated and ^#p < 0.05 vs. LPS (c); *p < 0.05 vs. untreated and ^#p < 0.05 vs. wild type. e, f Relative mRNA expression of ABCC2 in HuH7 cells left untreated or exposed to IL-1β (2 ng/ml) for 4 h with and without prior (1 h) exposure to NF-κB inhibitor (BAY-11-7082, 50 μM; designated as NF-κB in h) with and without transient transfection with an NF-κB repressor plasmid (NF-κB SR) (depicting mean ± SEM of technical triplicates from one representative out of at least five experiments). *p < 0.05 vs. all other groups by one-way ANOVA and Tukey's correction. g, h Chromatin immunoprecipitation (ChIP) on liver homogenate from WT chow, WT DSS/PN, and Il1r^−/−DSS/PN mice with specific antibodies for either FXR (left) or NF-κB p50 and p65 subunits (right) binding to the promotor of mouse Abcb11 (g) or the promotor of mouse Nr1h4 (h) represented as semi-quantitative data (top) and quantitative PCR data with specific primers (bottom). i Exemplary schematic depicting relative distance between binding sites for FXR and NF-κB within Abcb11 promoter