Effects of culture duration on gene expression of P450 isoforms, uptake and efflux transporters in primary hepatocytes cultured in the absence and presence of interleukin-6: Implications for experimental design for the evaluation of downregulatory effects of biotherapeutics

Current Drug Metabolism

Volumn 13, Issue 7, 2012, Pages 938-946

  Yang, Qian ^a   Doshi, Utkarsh ^a   Li, Nicole ^a   Li, Albert P ^a  

^a In Vitro ADMET Laboratories LLC   (United States)

Author keywords

Acute phase proteins; Biotherapeutics; Collagen matrigel sandwich cultures; Culture duration; Drug metabolism; Efflux transporters; Gene expression; Human hepatocytes; IL 6; P450; Uptake transporters

Indexed keywords

ACUTE PHASE PROTEIN; BREAST CANCER RESISTANCE PROTEIN; C REACTIVE PROTEIN; CARRIER PROTEIN; COLLAGEN; CYTOCHROME P450 1A2; CYTOCHROME P450 2B6; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; INTERLEUKIN 6; ISOENZYME; LIPOPOLYSACCHARIDE BINDING PROTEIN; MATRIGEL; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 4; ORGANIC ANION TRANSPORTER 2; ORGANIC ANION TRANSPORTER 3; ORGANIC CATION TRANSPORTER 1; PROTEIN ABCB11; PROTEIN ABCC2; PROTEIN ABCC3; PROTEIN ABCC4; PROTEIN SCL10A1; PROTEIN SLC22A7; PROTEIN SLCO2B1; SUPPRESSOR OF CYTOKINE SIGNALING 3; UNCLASSIFIED DRUG;

ARTICLE; CELL CULTURE; CONTROLLED STUDY; DOWN REGULATION; EVALUATION; GENE EXPRESSION; HUMAN; HUMAN CELL; LIVER CELL; PROTEIN INDUCTION; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION;

BIOLOGICAL AGENTS; CELL CULTURE TECHNIQUES; CELLS, CULTURED; CYTOCHROME P-450 ENZYME SYSTEM; DOWN-REGULATION; DRUG EVALUATION, PRECLINICAL; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HEPATOCYTES; HUMANS; INTERLEUKIN-6; ISOENZYMES; MEMBRANE TRANSPORT PROTEINS; MIDDLE AGED; TIME FACTORS;

EID: 84865767429     PISSN: 13892002     EISSN: 18755453     Source Type: Journal    
DOI: 10.2174/138920012802138570     Document Type: Article

References (30)

1. Morgan, E. T. Regulation of cytochromes P450 during inflammation and infection. Drug Metab. Rev., 1997, 29, 1129-1188.
2. Castell, J. V.; Gomez-Lechon, M. J.; David, M.; Fabra, R.; Trullenque, R.; Heinrich, P. C. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology, 1990, 12, 1179-1186.
3. Heinrich, P. C.; Castell, J. V.; Andus, T. Interleukin-6 and the acute phase response. Biochem. J., 1990, 265, 621-636.
4. Taub, R. Liver regeneration: from myth to mechanism. Nat. Rev. Mol. Cell Biol., 2004, 5, 836-847.
5. Siewert, E.; Dietrich, C. G.; Lammert, F.; Heinrich, P. C.; Matern, S.; Gartung, C.; Geier, A. Interleukin-6 regulates hepatic transporters during acute-phase response. Biochem. Biophys. Res. Commun., 2004, 322, 232-238.
6. Geier, A.; Dietrich, C. G.; Voigt, S.; Ananthanarayanan, M.; Lammert, F.; Schmitz, A.; Trauner, M.; Wasmuth, H. E.; Boraschi, D.; Balasubramaniyan, N.; Suchy, F. J.; Matern, S.; Gartung, C. Cytokine-dependent regulation of hepatic organic anion transporter gene transactivators in mouse liver. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 289, G831-841.
7. Aitken, A. E.; Morgan, E. T. Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. Drug Metab. Dispos., 2007, 35, 1687-1693.
8. Dickmann, L. J.; Patel, S. K.; Rock, D. A.; Wienkers, L. C.; Slatter, J. G. Effects of Interleukin 6 (IL-6) and an anti-IL-6 Monoclonal Antibody on Drug Metabolizing Enzymes in Human Hepatocyte Culture. Drug Metab. Dispos., 2011, 39(8), 1415-22.
9. Vee, M. L.; Lecureur, V.; Stieger, B.; Fardel, O. Regulation of drug transporter expression in human hepatocytes exposed to the proinflammatory cytokines tumor necrosis factor-alpha or interleukin-6. Drug Metab. Dispos., 2009, 37, 685-693.
10. Diao, L.; Li, N.; Brayman, T. G.; Hotz, K. J.; Lai, Y. Regulation of MRP2/ABCC2 and BSEP/ABCB11 expression in sandwich cultured human and rat hepatocytes exposed to inflammatory cytokines TNF-{alpha}, IL-6, and IL-1{beta}. J. Biol. Chem., 2010, 285, 31185-31192.
11. Morgan, E. T. Regulation of cytochrome p450 by inflammatory mediators: why and how?, Drug Metab. Dispos., 2001, 29, 207-212
12. Slaviero, K. A.; Clarke, S. J.; Rivory, L. P. Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol., 2003, 4, 224-232.
13. Morgan, E. T.; Goralski, K. B.; Piquette-Miller, M.; Renton, K. W.; Robertson, G. R.; Chaluvadi, M. R.; Charles, K. A.; Clarke, S. J.; Kacevska, M.; Liddle, C.; Richardson, T. A.; Sharma, R.; Sinal, C. J. Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer. Drug Metab. Dispos., 2008, 36, 205-216.
14. Aitken, A. E.; Richardson, T. A.; Morgan, E. T. Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu. Rev. Pharmacol. Toxicol., 2006, 46, 123-149.
15. Morgan, E. T. Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clin. Pharmacol. Ther., 2009, 85, 434-438.
16. Fahmi, O. A.; Kish, M.; Boldt, S.; Obach, R. S. Cytochrome P450 3A4 mRNA is a more reliable marker than CYP3A4 activity for detecting pregnane X receptor-activated induction of drug-metabolizing enzymes. Drug Metab. Dispos., 2010, 38, 1605-1611.
17. Lee, C. M.; Pohl, J.; Morgan, E. T. Dual mechanisms of CYP3A protein regulation by proinflammatory cytokine stimulation in primary hepatocyte cultures. Drug Metab. Dispos., 2009, 37, 865-872.
18. Boess, F.; Kamber, M.; Romer, S.; Gasser, R.; Muller, D.; Albertini, S.; Suter, L. Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in vivo liver gene expression in rats: possible implications for toxicogenomics use of in vitro systems. Toxicol. Sci., 2003, 73, 386-402.
19. Ferrini, J. B.; Pichard, L.; Domergue, J.; Maurel P. Long-term primary cultures of adult human hepatocytes. Chem. Biol. Interact., 1997, 107, 31-45.
20. Ulvestad, M.; Bjorquist, P.; Molden, E.; Asberg, A.; Andersson, T. B. OATP1B1/1B3 activity in plated primary human hepatocytes over time in culture. Biochem. Pharmacol., 2011. 82(9), 1219-26.
21. Bi, Y. A.; Kazolias, D.; Duignan, D. B. Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport. Drug Metab. Dispos., 2006, 34, 1658-1665.
22. Renton, K. W. Alteration of drug biotransformation and elimination during infection and inflammation. Pharmacol. Ther., 2001, 92, 147-163.
23. Renton, K. W. Cytochrome P450 regulation and drug biotransformation during inflammation and infection. Curr. Drug Metab., 2004, 5, 235-243.
24. Renton, K. W. Regulation of drug metabolism and disposition during inflammation and infection. Expert. Opin. Drug Metab. Toxicol., 2005, 1, 629-640.
25. Morgan, E. T.; Li-Masters, T.; Cheng, P. Y. Mechanisms of cytochrome P450 regulation by inflammatory mediators. Toxicology. 2002, 181-182, 207-210.
26. Teng, S.; Piquette-Miller, M. The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice. J. Pharmacol. Exp. Ther., 2005, 312, 841-848.
27. Beigneux, A. P.; Moser, A. H.; Shigenaga, J. K.; Grunfeld, C.; Feingold, K. R. Reduction in cytochrome P-450 enzyme expression is associated with repression of CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse liver during the acute phase response. Biochem. Biophys. Res. Commun., 2002, 293, 145-149.
28. Pascussi, J. M.; Gerbal-Chaloin, S.; Pichard-Garcia, L.; Daujat, M.; Fabre, J. M.; Maurel, P.; Vilarem, M. J. Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes. Biochem. Biophys. Res. Commun., 2000, 274, 707-713.
29. Hu, Y.; Yang, S.; Shilliday, F. B.; Heyde, B. R.; Mandrell, K. M.; Robins, R. H.; Xie, J.; Reding, M. T.; Lai, Y.; Thompson, D. C. Novel metabolic bioactivation mechanism for a series of antiinflammatory agents (2,5-diaminothiophene derivatives) mediated by cytochrome p450 enzymes. Drug Metab. Dispos., 2010, 38, 1522-1531.
30. Aitken, A. E.; Lee, C. M.; Morgan, E. T. Roles of nitric oxide in inflammatory downregulation of human cytochromes P450. Free Radic. Biol. Med., 2008, 44, 1161-1168.