Abstract
Expression and activities of cytochrome P450 enzymes are down-regulated in the liver during the host response to inflammation or infection, leading to alterations in drug clearance and toxin activation. This review focuses on recent studies on the mechanisms of this down-regulation, as well as the cytokines and cell types involved. Possible reasons for cytochrome P450 down-regulation are discussed.
Footnotes
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Send reprint requests to: Edward T. Morgan, Ph.D., Department of Pharmacology, Emory University, 1510 Clifton Rd., Atlanta, GA 30322. E-mail: etmorga{at}bimcore.emory.edu
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This work was supported by Grants GM46897 and GM53093 from the National Institute of General Medical Sciences.
- Abbreviations used are::
- P450
- cytochrome P450
- LPS
- bacterial lipopolysaccharide
- NO
- nitric oxide
- NOS2
- inducible NO synthase
- EET
- epoxyeicosatrienoic acid
- TNFα
- tumor necrosis factor-α
- IL
- interleukin
- NF
- nuclear factor
- PPARα
- peroxisome proliferator-activated receptor-α
- Received October 11, 2000.
- Accepted December 12, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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Regulation of Cytochrome P450 by Inflammatory Mediators: Why and How?
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- Article
- Abstract
- Causes of Interindividual Variation in Drug Metabolism
- Regulation of P450 by Inflammation and Infection
- Rodent Models and Human Studies
- P450 Down-Regulation: A Homeostatic Mechanism or a Pathophysiological Phenomenon?
- Humoral Factors and Cell Types Involved in P450 Down-Regulation
- Molecular Mechanisms of Down-Regulation
- Conclusion
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