Regulation of Cytochrome P450 by Inflammatory Mediators: Why and How?

  1. Edward T. Morgan
  1. Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia

    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

    • 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

    • 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.
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