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Molecular Pharmacology

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Abstract

Induction of cytochrome P450 2E1 expression in rat and gerbil astrocytes by inflammatory factors and ischemic injury.

N Tindberg, H A Baldwin, A J Cross and M Ingelman-Sundberg
Molecular Pharmacology November 1996, 50 (5) 1065-1072;
N Tindberg
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H A Baldwin
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A J Cross
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M Ingelman-Sundberg
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Abstract

Hepatic cytochromes P450 are known to be down-regulated by cytokines, lipopolysaccharide, Gram-positive bacteria, and viruses. Little is known, however, about the regulation by inflammation of cytochromes P450 in other tissues. We have found that lipopolysaccharide and interleukin-1 beta stimulate the expression of catalytically active CYP2E1 (but not CYP1A1 or CYP2B) up to 7-fold in rat brain primary cortical glial cultures. The induction reached a maximum after 24 hr and was accompanied by an increase in CYP2E1 mRNA. Chlormethiazole, a specific inhibitor of hepatic CYP2E1 transcription, completely inhibited the induction of CYP2E1 at the mRNA and enzyme levels. Immunofluorescence studies showed CYP2E1 to be expressed in a subset of astrocytes in the lipopolysaccharide-stimulated cortical glial cultures. Using a model of global ischemic injury in the gerbil, we found CYP2E1 to be induced in vivo in astrocytes in the inflammatory phase, 1-3 weeks after the lesion. Likewise, CYP2E1 was induced in the rat cortex 1 week after a focal ischemic injury. Our results suggest tissue-specific regulation of CYP2E1 by inflammatory factors and that CYP2E1 may play a role in astrocytes during inflammation in the brain.

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Molecular Pharmacology
Vol. 50, Issue 5
1 Nov 1996
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Abstract

Induction of cytochrome P450 2E1 expression in rat and gerbil astrocytes by inflammatory factors and ischemic injury.

N Tindberg, H A Baldwin, A J Cross and M Ingelman-Sundberg
Molecular Pharmacology November 1, 1996, 50 (5) 1065-1072;

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Abstract

Induction of cytochrome P450 2E1 expression in rat and gerbil astrocytes by inflammatory factors and ischemic injury.

N Tindberg, H A Baldwin, A J Cross and M Ingelman-Sundberg
Molecular Pharmacology November 1, 1996, 50 (5) 1065-1072;
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