![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 288, Issue 3, 945-950, March 1999
Receptor (p55/p75) Knockout Mice After Endotoxin
Administration1
Graduate Center for Toxicology (G.W.W., R.A.B.),
Hepatic cytochromes P-450 (CYP) are well characterized drug and
xenobiotic metabolizing enzymes that are extensively regulated by
genetic and environmental factors. Inflammatory mediators, including
interleukins (ILs), interferons (IFNs), and tumor necrosis factor-
(TNF-), have been shown to down-regulate several CYP isoforms;
however, elucidation of the inflammatory mediators that are responsible
for specific CYP down-regulation is difficult. The purpose of this
experiment was to evaluate the role endogenous TNF- plays in the
regulation of liver CYP expression after endotoxin administration. Mice
deficient in the p55 and p75 TNF receptors and wild-type mice were
given Gram-negative bacterial lipopolysaccharide (LPS) and killed
24 h after administration. CYP analysis indicates that LPS
decreases CYP1A, CYP2B, CYP3A, and CYP4A independently of TNF-.
CYP2D9 and CYP2E1 activities show differential responses to LPS between
wild-type and TNF p55/p75 receptor knockout mice, indicating the
down-regulation of CYP2D9 and CYP2E1 is differentially modulated by
TNF- expression. Furthermore, TNF- appears to affect the
constitutive expression of CYP2D9 and CYP2E1. To date, this is the
first evidence suggesting that a proinflammatory cytokine is involved
in the constitutive regulation of drug-metabolizing enzymes.
0022-3565/99/2883-0945$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics
This article has been cited by other articles:
|
|
 |
|
  R. Vuppugalla and R. Mehvar SELECTIVE EFFECTS OF NITRIC OXIDE ON THE DISPOSITION OF CHLORZOXAZONE AND DEXTROMETHORPHAN IN ISOLATED PERFUSED RAT LIVERS Drug Metab. Dispos., July 1, 2006; 34(7): 1160 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Goralski, D. Abdulla, C. J. Sinal, A. Arsenault, and K. W. Renton Toll-like receptor-4 regulation of hepatic Cyp3a11 metabolism in a mouse model of LPS-induced CNS inflammation Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G434 - G443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Richardson and E. T. Morgan Hepatic Cytochrome P450 Gene Regulation during Endotoxin-Induced Inflammation in Nuclear Receptor Knockout Mice J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 703 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vuppugalla and R. Mehvar ENZYME-SELECTIVE EFFECTS OF NITRIC OXIDE ON AFFINITY AND MAXIMUM VELOCITY OF VARIOUS RAT CYTOCHROMES P450 Drug Metab. Dispos., June 1, 2005; 33(6): 829 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Li and C. D. Klaassen Lipopolysaccharide-Induced Down-Regulation of Organic Anion Transporting Polypeptide 4 (Oatp4; Slc21a10) Is Independent of Tumor Necrosis Factor-{alpha}, Interleukin-1{beta}, Interleukin-6, or Inducible Nitric Oxide Synthase Toxicol. Sci., January 1, 2005; 83(1): 197 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vuppugalla and R. Mehvar Hepatic Disposition and Effects of Nitric Oxide Donors: Rapid and Concentration-Dependent Reduction in the Cytochrome P450-Mediated Drug Metabolism in Isolated Perfused Rat Livers J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 718 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pan, Q. Xiang, S. Ball, J. Scatina, J. Kao, and J.-Y. Hong Lipopolysaccharide-Mediated Modulation of Cytochromes P450 in Stat1 Null Mice Drug Metab. Dispos., April 1, 2003; 31(4): 392 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hakkola, Y. Hu, and M. Ingelman-Sundberg Mechanisms of Down-Regulation of CYP2E1 Expression by Inflammatory Cytokines in Rat Hepatoma Cells J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1048 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Van Ess, M. P. Mattson, and R. A. Blouin Enhanced Induction of Cytochrome P450 Enzymes and CAR Binding in TNF (p55-/-/p75-/-) Double Receptor Knockout Mice Following Phenobarbital Treatment J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 824 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Morgan Regulation of Cytochrome P450 by Inflammatory Mediators: Why and How? Drug Metab. Dispos., March 1, 2001; 29(3): 207 - 212. [Abstract] [Full Text]
|
|
|
|
|
|
C. C. Barton, P. E. Ganey, and R. A. Roth Lipopolysaccharide Augments Aflatoxin B1-Induced Liver Injury through Neutrophil-Dependent and -Independent Mechanisms Toxicol. Sci., November 1, 2000; 58(1): 208 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pan, Q. Xiang, and S. Ball Use of a Novel Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction Method to Study the Effects of Cytokines on Cytochrome P450 mRNA Expression in Mouse Liver Drug Metab. Dispos., June 1, 2000; 28(6): 709 - 713. [Abstract] [Full Text]
|
|
|
|
|
|
T. L. Horn, T. D. O'Brien, L. B. Schook, and M. S. Rutherford Acute Hepatotoxicant Exposure Induces TNFR-Mediated Hepatic Injury and Cytokine/Apoptotic Gene Expression Toxicol. Sci., March 1, 2000; 54(1): 262 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Rockich and R. Blouin Effect of the Acute-Phase Response on the Pharmacokinetics of Chlorzoxazone and Cytochrome P-450 2E1 In Vitro Activity in Rats Drug Metab. Dispos., September 1, 1999; 27(9): 1074 - 1077. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
