TABLE 1. Effects of CsA and FK506 on Expression of mRNAs Encoding Genes Related to Hepatobiliary Transporters, Nuclear Receptors, and Phase I Metabolizing Enzymes in HepaRG Cells After 24 h Exposure.
| CSA 1μM | CSA 5μM | CsA 10μM | CsA 25μM | CsA 50μM | FK506 1μM | FK506 5μM | FK506 10μM | FK506 25μM | FK506 50μM | |
|---|---|---|---|---|---|---|---|---|---|---|
| Nuclear receptors | ||||||||||
| FXR | 1.27±0.05* | 1.18±0.09 | 1.05±0.18 | 0.88±0.05 | 0.69±0.09* | 1.045±0.25 | 1.44±0.33 | 1.64±0.68 | 1.173±0.20 | 0.95±0.21 |
| PXR | 1.39±0.1 | 1.94±0.13*** | 1.14±0.14 | 0.44±0.07*** | 0.32±0.02*** | 1.07±0.08 | 1.15±0.09 | 0.83±0.02 | 0.94±0.04 | 0.58±0.12*** |
| CAR | 1.4±0.1* | 1.25±0.55 | 1.01±0.30 | 0.4±0.03*** | 0.04±0.02*** | 1.03±0.44 | 1.44±0.40 | 0.81±0.21 | 0.76±0.18** | 0.30±0.18** |
| BA transporters | ||||||||||
| BSEP | 1.09±0.09 | 1.01±0.15 | 0.79±0.17 | 0.61±0.11** | 0.54±0.15** | 1.17±0.03 | 0.76±0.22 | 0.77±0.14 | 0.72±0.11* | 0.63±0.11** |
| BCRP | 1.19±0.08 | 2.14±0.11*** | 2.51±0.50 | 2.76±0.09*** | 3.36±0.85* | 0.92±0.15 | 0.95±0.13 | 0.95±0.13 | 1.02±0.12 | 1.74±0.42 |
| MDR3 | 1.26±0.34 | 1.161±0.11 | 0.93±0.17 | 0.34±0.09*** | 0.23±0.05*** | 0.95±0.13 | 0.89±0.21 | 0.6±0.15 | 0.39±0.09** | 0.47±0.18* |
| MRP2 | 0.9±0.24 | 1.06±0.21 | 1.3±0.18* | 1.80±0.14*** | 1.8±0.15*** | 0.90±0.12 | 1.35±0.3 | 1.34±0.28 | 1.58±0.15* | 2.04±0.41* |
| MRP3 | 1.02±0.11 | 1.4±0.18** | 1.50±0.14*** | 1.57±0.07*** | 1.79±0.08*** | 1.18±0.13 | 1.371±0.41 | 1.41±0.43 | 1.6±0.23* | 1.64±0.32* |
| MRP4 | 0.99±0.18 | 1.44±0.21 | 1.55±0.18* | 2.8±0.09*** | 2.68±0.12*** | 1.34±0.17 | 1.68±0.03*** | 1.8±0.05*** | 1.8±0.09* | 2.60±0.51* |
| NTCP | 2.16±0.55* | 2.64±0.54** | 1.51±0.33 | 0.10±0.02*** | 0.05±0.01*** | 1.11±0.24 | 1.3±0.23 | 0.82±0.09 | 0.45±0.15*** | 0.23±0.08*** |
| BA metabolizing enzymes | ||||||||||
| CYP27A1 | 0.88±0.04 | 1.04±0.07 | 0.86±0.03 | 0.53±0.05*** | 0.41±0.08*** | 1.00±0.16 | 1.16±0.35 | 0.86±0.11 | 1.3±0.46 | 0.47±0.06*** |
| CYP8B1 | 0.84±0.27 | 1.15±0.14 | 0.73±0.24 | 0.26±0.08 | 0.05±0.01 | 1.5±0.25 | 1.62±0.71 | 1.03±0.35 | 0.77±0.08** | 0.32±0.1*** |
| CYP7A1 | 1.08±0.03 | 1.11±0.07 | 1.11±0.05 | 0.92±0.01** | 0.42±0.13** | 1.06±0.29 | 1.42±0.37 | 0.87±0.08 | 1.4±0.11 | 0.9±0.12* |
| CYP3A4 | 1.62±0.05*** | 1.51±0.28* | 1.33±0.57 | 0.23±0.05*** | 0.12±0.01*** | 1.3±0.23 | 1.8±0.21** | 1.54±0.18* | 0.93±0.13 | 0.34±0.08*** |
Note: Data represent the means ± SD of three independent experiments. All results are expressed relative to the levels found in untreated cells, arbitrarily set at a value of 1. *p < 0.05, **p < 0.01, ***p < 0.001 compared with non-treated cells.