Inflammatory processes are associated with compromised metabolism and elimination of drugs in the liver, largely mediated by proinflammatory cytokines, such as @entity650 . The Hepa-RG cell line is an established surrogate for primary @entity1 hepatocytes (PHH) in drug metabolism and @entity137 studies. However, the impact of inflammatory signaling on HepaRG cells has not been well characterized. In this study, the response of primary @entity1 hepatocytes and HepaRG cells to @entity650 was comparatively analyzed. For this purpose, broad-spectrum gene expression profiling, including acute-phase response genes and a large panel of drug-metabolizing enzyme and transporter (DMET) genes as well as their modifiers and regulators, was conducted in combination with cytochrome P450 (P450) activity measurements. Exposure of PHH and HepaRG cells to @entity650 resulted in highly similar coordinated reduction of DMET mRNA, including major @entity855 -binding cassette transporters (ABCs), P450s, glutathione S-transferases (GSTs), @entity858 glucuronosyltransferases (UGTs), and @entity46411 ( @entity46411 ). Enzyme activities of @entity4914 , @entity11670 , @entity12327 , @entity5060 , @entity4433 , and @entity5322 were reduced upon 48-72 hours exposure to @entity650 in PHH and HepaRG. However, although these effects were not significant in PHH due to large interindividual donor variability, the impact on HepaRG was more pronounced and highly significant, thus emphasizing the advantage of HepaRG as a more reproducible model system. Exposure of HepaRG cells to @entity1356 and @entity5 @entity39 factor a resulted in similar effects on gene expression and enzyme activities. The present study emphasizes the role of proinflammatory cytokines in the regulation of drug metabolism and supports the use of HepaRG in lieu of PHH to minimize subject variability.

A Systematic Comparison of the Impact of Inflammatory Signaling on Absorption, Distribution, Metabolism, and Excretion Gene Expression and Activity in Primary XXXX Hepatocytes and HepaRG Cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity650 :: ('3569', 'Gene') :: ['IL-6', 'interleukin-6', 'interleukin (IL)-6'] @entity11670 :: ('1555', 'Gene') :: ['CYP2B6'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity46411 :: ('MESH:C563665', 'Disease') :: ['SLCs', 'solute carriers'] @entity4433 :: ('1557', 'Gene') :: ['CYP2C19'] @entity5322 :: ('1576', 'Gene') :: ['CYP3A4'] @entity1356 :: ('3553', 'Gene') :: ['interleukin-1b'] @entity858 :: ('MESH:D014530', 'Chemical') :: ['uridine diphosphate'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis'] @entity5060 :: ('1559', 'Gene') :: ['CYP2C9'] @entity12327 :: ('1558', 'Gene') :: ['CYP2C8'] @entity4914 :: ('1544', 'Gene') :: ['CYP1A2'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity1 :: (9606,Species) :: ['Human']
