Effects of IL-6, LPS, and ANC28.1 on P450 mRNA expression and enzyme activities in human hepatocytes in vitro
| Treatment | Cultures Used in LPS Experiments (n = 3) | Cultures Used in ANC28.1 Experiments (n = 3) |
|---|---|---|
| CYP1A2 | ||
| P450 mRNA (RQFa) | ||
| Medium | 1.00 ± 0.00b | 1.00 ± 0.00 |
| IL-6 (10 ng/ml) | 0.831 ± 0.791 | 0.280 ± 0.115 |
| LPS (25 ng/ml) | 0.617 ± 0.150 | NA |
| ANC28.1 (2 μg/ml) | NA | 1.17 ± 0.172 |
| P450 activity (% of control) | ||
| Medium | 100% (value = 43.9 ± 12.8 ng/ml)c | 100% (value = 45.3 ± 21.6 ng/ml) |
| IL-6 (10 ng/ml) | 34.7 ± 7.31 | 30.3 ± 9.50 |
| LPS (25 ng/ml) | 45.9 ± 15.6 | NA |
| ANC28.1 (2 μg/ml) | NA | 85.2 ± 22.4 |
| CYP2B6 | ||
| P450 mRNA (RQF) | ||
| Medium | 1.00 ± 0.00 | 1.00 ± 0.00 |
| IL-6 (10 ng/ml) | 0.240 ± 0.166 | 0.400 ± 0.170 |
| LPS (25 ng/ml) | 0.439 ± 0.0877 | NA |
| ANC28.1 (2 μg/ml) | NA | 1.09 ± 0.354 |
| P450 activity (% of control) | ||
| Medium | 100% (value = 77.3 ± 30.3 ng/ml) | 100% (value = 55.2 ± 18.4 ng/ml) |
| IL-6 (10 ng/ml) | 34.3 ± 1.40 | 55.0 ± 24.5 |
| LPS (25 ng/ml) | 89.8 ± 61.9 | NA |
| ANC28.1 (2 μg/ml) | NA | 82.5 ± 21.3 |
| CYP3A4 | ||
| P450 mRNA (RQF) | ||
| Medium | 1.00 ± 0.00 | 1.00 ± 0.00 |
| IL-6 (10 ng/ml) | 0.00433 ± 0.00404 | 0.0667 ± 0.0808 |
| LPS (25 ng/ml) | 0.0230 ± 0.0283 | NA |
| ANC28.1 (2 μg/ml) | NA | 0.673 ± 0.454 |
| P450 activity (% of control) | ||
| Medium | 100% (value = 477 ± 132 ng/ml) | 100% (value = 260 ± 26.6 ng/ml) |
| IL-6 (10 ng/ml) | 16.6 ± 17.4 | 24.3 ± 1.70 |
| LPS (25 ng/ml) | 28.6 ± 11.2 | NA |
| ANC28.1 (2 μg/ml) | NA | 88.9 ± 19.0 |
NA, not applicable; RQF, relative quantification factor.
↵a RQF is a measure of a change in mRNA expression in a test sample relative to that in a control sample (e.g., medium).
↵b Values are the mean ± standard deviation of triplicate determinations of RQF.
↵c Values are the mean ± standard deviation of triplicate determinations of phenacetin O-dealkylation (CYP1A2), bupropion hydroxylation (CYP2B6), or midazolam 1´-hydroxylation (CYP3A) expressed as percent of control (medium alone).