Hepatic Cytochrome P-450 Expression in Tumor Necrosis Factor-α Receptor (p55/p75) Knockout Mice After Endotoxin Administration

摘要: Hepatic cytochromes P-450 (CYP) are well characterized drug and xenobiotic metabolizing enzymes that extensively regulated by genetic environmental factors. Inflammatory mediators, including interleukins (ILs), interferons (IFNs), tumor necrosis factor-α (TNF-α), have been shown to down-regulate several CYP isoforms; however, elucidation of the inflammatory mediators responsible for specific down-regulation is difficult. The purpose this experiment was evaluate role endogenous TNF-α plays in regulation liver expression after endotoxin administration. Mice deficient p55 p75 TNF receptors wild-type mice were given Gram-negative bacterial lipopolysaccharide (LPS) killed 24 h analysis indicates LPS decreases CYP1A, CYP2B, CYP3A, CYP4A independently TNF-α. CYP2D9 CYP2E1 activities show differential responses between p55/p75 receptor knockout mice, indicating differentially modulated expression. Furthermore, appears affect constitutive CYP2E1. To date, first evidence suggesting a proinflammatory cytokine involved drug-metabolizing enzymes.