Effects of rifampicin siHNF4 versus scrambled siRNA and rifampin on CYP2C8, CYP2C9, and CYP2C19 mRNA in primary human hepatocytes infected with scrambled siRNA or siHNF4-I
Expression of CYP2C8, CYP2C9, CYP2C19, and HNF4α mRNAs was evaluated in primary human hepatocytes in triplicate from four different donors after infection with adenovirus containing scrambled siRNA or siHNF4-I in the presence of 0.2% DMSO or 10 μM rifampicin. Data are expressed as fold induction over the DMSO controls and represent the mean ± S.D. of the four donors. Values were compared using Mann-Whitney tests.
Treatment | HNF4 | 2C8 | 2C9 | 2C19 | ||||
---|---|---|---|---|---|---|---|---|
DMSO | Rif | DMSO | Rif | DMSO | Rif | DMSO | Rif | |
SCR | 1.00 ± 0.00 | 1.06 ± 0.11 | 1.00 ± 0.00 | 6.58 ± 1.79a | 1.00 ± 0.00 | 3.00 ± 0.70a | 1.00 ± 0.00 | 1.84 ± 0.31a |
siHNF4 | 0.31 ± 0.09b | 0.40 ± 0.10a,b | 0.47 ± 0.06b | 1.09 ± 0.45a,b | 0.45 ± 0.14b | 0.63 ± 0.14b | 0.57 ± 0.15b | 0.66 ± 0.24b |
SCR, scrambled; Rif, rifampin.
↵a Values from cells treated with rifampicin significantly higher than those treated with DMSO for cells infected with scrambled siRNA or siHNF4-I, p < 0.05.
↵b Values from cells treated with siHNF4-I significantly lower than those treated with SCR siRNA for either DMSO or rifampicin controls, p < 0.05.