Effects of monocyte chemoattractant protein ‐1, macrophage inflammatory protein‐1α, and interferon‐α2a on P450 enzymes in human hepatocytes in vitro

This study sought to identify which cytokines were responsible for tilsotolimod's indirect effects on P450 enzymes in vitro. A 72‐h treatment with recombinant human chemokines MCP‐1 and MIP‐1α did not alter CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP3A4, or signal transducer and activator of transcription 1 (STAT1) mRNA expression or CYP1A2, CYP2B6, or CYP3A4/5 enzyme activity in cocultures of huma n hepatocytes and Kupffer cells. INF‐α2a, at 2.5 ng/mL but not at the lower concentrations applied to the cells, increased CYP1A2 and STAT1 mRNA by 2.4‐ and 5.2‐fold, respectively, and reduced CYP2B6 enzyme activity to 46% of control. This study established that INF‐α2a, but not MCP‐1 o r MIP‐1α, mediated tilsotolimod effects on CYP1A2 and CYP2B6 expression in human hepatocytes.
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research