Abstract
We have investigated the effects of interleukin (IL)-1 beta and IL6 on expression and phenobarbital (PB) induction of ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-deethylase (PROD) activities, as well as on mRNA levels of cytochromes P450 (CYP) 1A, 2B, 2C, 2E and 3A, in rat hepatocytes in primary culture. IL6 slightly antagonized PB-induced PROD activity. Strikingly, IL1 beta strongly inhibited basal EROD and PROD activities, and fully blocked their induction by PB in a dose-dependent fashion. Furthermore IL1 beta completely suppressed PB induction of all CYP mRNAs analyzed. Our results demonstrate that IL1 beta can suppress basal CYP activities, as well as PB-inducible expression of five CYP mRNAs in rat hepatocytes in primary culture.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Cytochrome P-450 CYP1A1
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Cytochrome P-450 CYP2B1
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Cytochrome P-450 Enzyme System / biosynthesis*
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Cytochrome P-450 Enzyme System / genetics
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Enzyme Induction / drug effects
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Humans
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Interleukin-1 / pharmacology*
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Interleukin-6 / pharmacology
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Liver / drug effects*
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Liver / enzymology
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Male
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Oxidoreductases / biosynthesis
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Oxidoreductases / genetics
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Phenobarbital / antagonists & inhibitors*
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / pharmacology
Substances
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Interleukin-1
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Interleukin-6
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RNA, Messenger
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Recombinant Proteins
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Cytochrome P-450 Enzyme System
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Oxidoreductases
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Cytochrome P-450 CYP1A1
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Cytochrome P-450 CYP2B1
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Phenobarbital