Effects of inflammatory cytokines on the expression levels of drug-metabolizing enzymes and transporters in primary cultured human hepatocytes
| IL-1β | IL-2 | IL-6 | IFNγ | TGFβ | TNFα | |
|---|---|---|---|---|---|---|
| NTCP | ↓ (mRNA) (Le Vee et al., 2008) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA, protein) (Le Vee et al., 2009) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | ↓ (mRNA, protein) (Le Vee et al., 2009) | ||
| OAT2 | → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2009) → (mRNA) (Nguyen et al., 2015) | → (mRNA) (Le Vee et al., 2011) | ↓ (mRNA) (Le Vee et al., 2009) | ||
| OATP1B1 | ↓ (mRNA, protein) (Le Vee et al., 2008) ↓ (mRNA, protein) (Le Vee et al., 2009) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA, protein) (Le Vee et al., 2009) → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | ↓ (mRNA, protein) (Le Vee et al., 2009) | ||
| OATP1B3 | ↓ (mRNA) (Le Vee et al., 2008) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2009) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | ↓ (mRNA) (Le Vee et al., 2009) | ||
| OATP2B1 | ↓ (mRNA) (Le Vee et al., 2008) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2009) → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | ↓ (mRNA) (Le Vee et al., 2009) | ||
| OCT1 | ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2009) ↓ (mRNA) (Nguyen et al., 2015) | → (mRNA) (Le Vee et al., 2011) | ↓ (mRNA) (Le Vee et al., 2009) | ||
| MRP2 | ↓ (mRNA) (Le Vee et al., 2008) ↓ (mRNA, protein) (Diao et al., 2010) | ↓ (mRNA, protein) (Le Vee et al., 2009) ↓ (mRNA, protein) (Diao et al., 2010) → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | → (mRNA) (Le Vee et al., 2009) ↓ (mRNA, protein) (Diao et al., 2010) | ||
| MRP3 | ↓ (mRNA) (Le Vee et al., 2008) → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA), ↑ (protein) (Le Vee et al., 2009) → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | → (mRNA), ↑ (protein) (Le Vee et al., 2009) | ||
| MRP4 | ↓ (mRNA) (Le Vee et al., 2008) | ↓ (mRNA) (Le Vee et al., 2009) | → (mRNA) (Le Vee et al., 2009) | |||
| BCRP | ↓ (mRNA) (Le Vee et al., 2008) | ↓ (mRNA, protein) (Le Vee et al., 2009) | ↓ (mRNA) (Le Vee et al., 2011) | → (mRNA), ↑ (protein) (Le Vee et al., 2009) | ||
| BSEP | ↓ (mRNA) (Le Vee et al., 2008) ↓ (mRNA), ↑ (protein) (Diao et al., 2010) ↓ (mRNA) (Nguyen et al., 2015) | → (mRNA) (Le Vee et al., 2009) ↓ (mRNA), ↑ (protein) (Diao et al., 2010) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | ↓ (mRNA) (Le Vee et al., 2009) ↓ (mRNA), → (protein) (Diao et al., 2010) | ||
| P-gp | → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA), → (protein) (Le Vee et al., 2009) → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Le Vee et al., 2011) | → (mRNA, protein) (Le Vee et al., 2009) | ||
| CYP1A2 | ↓ (mRNA, protein) (Muntané-Relat et al., 1995) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (protein) (Elkahwaji et al., 1999) | ↓ (mRNA, protein) (Muntané-Relat et al., 1995) ↓ (mRNA) (Dickmann et al., 2011) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA, protein) (Muntané-Relat et al., 1995) | ||
| CYP2A6 | → (mRNA) (Kleine et al., 2008) | |||||
| CYP2B6 | → (mRNA), ↓ (protein) (Aitken and Morgan, 2007) → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA, protein) (Aitken and Morgan, 2007) ↓ (mRNA) (Dickmann et al., 2011) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA), ↓/→ (protein) (Aitken and Morgan, 2007) | ↑ (mRNA), ↓ (protein) (Aitken and Morgan, 2007) | → (mRNA), ↓ (protein) (Aitken and Morgan, 2007) | |
| CYP2C8 | ↓ (mRNA) (Aitken and Morgan, 2007) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (protein as CYP2C) (Elkahwaji et al., 1999) | ↓ (mRNA) (Kleine et al., 2008) ↓ (mRNA) (Aitken and Morgan, 2007) ↓ (mRNA) (Dickmann et al., 2011) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Aitken and Morgan, 2007) | ↓ (mRNA) (Aitken and Morgan, 2007) | ↓ (mRNA) (Aitken and Morgan, 2007) |
| CYP2C9 | → (mRNA), ↓/→ (protein) (Aitken and Morgan, 2007) → (mRNA) (Nguyen et al., 2015) | ↓ (protein as CYP2C) (Elkahwaji et al., 1999) | ↓ (mRNA, protein) (Aitken and Morgan, 2007) ↓ (mRNA) (Nguyen et al., 2015) | → (mRNA) (Aitken and Morgan, 2007) | ↓ (mRNA), ↓/→ (protein) (Aitken and Morgan, 2007) | → (mRNA), ↓ (protein) (Aitken and Morgan, 2007) |
| CYP2C19 | ↓ (mRNA) (Aitken and Morgan, 2007) | ↓ (protein as CYP2C) (Elkahwaji et al., 1999) | → (mRNA) (Aitken and Morgan, 2007) ↓ (mRNA) (Dickmann et al., 2011) → (mRNA) (Nguyen et al., 2015) | → (mRNA) (Aitken and Morgan, 2007) | ↓ (mRNA) (Aitken and Morgan, 2007) | → (mRNA) (Aitken and Morgan, 2007) |
| CYP2D6 | → (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Dickmann et al., 2011) → (mRNA) (Nguyen et al., 2015) | ||||
| CYP2E1 | → (mRNA) (Nguyen et al., 2015) | ↓ (protein) (Elkahwaji et al., 1999) | → (mRNA) (Nguyen et al., 2015) | |||
| CYP3A4 | ↓ (mRNA, protein) (Muntané-Relat et al., 1995) ↓ (mRNA, protein) (Aitken and Morgan, 2007) → (mRNA) (Nguyen et al., 2015) | ↓ (protein) (Elkahwaji et al., 1999) | ↓ (mRNA, protein) (Muntané-Relat et al., 1995) ↓ (mRNA) (Kleine et al., 2008) ↓ (mRNA, protein) (Aitken and Morgan, 2007) ↓ (mRNA) (Dickmann et al., 2011) ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA, protein) (Aitken and Morgan, 2007) | ↓ (mRNA, protein) (Aitken and Morgan, 2007) | ↓ (mRNA, protein) (Muntané-Relat et al., 1995) ↓ (mRNA, protein) (Aitken and Morgan, 2007) |
| UGT1A1 | ↓ (mRNA) (Nguyen et al., 2015) | ↓ (mRNA) (Nguyen et al., 2015) |
IFNγ, interferon-γ; P-gp, P-glycoprotein; TGFβ, transforming growth factor-β; TNFα, tumor necrosis factor-α.