Interleukin‐1β antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture

Abdel-Razzak, Ziad; Corcos, Laurent; Fautrel, Alain; Guillouzo, André

doi:10.1016/0014-5793(95)00513-9

Cited by 60 publications

(50 citation statements)

References 41 publications

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“…Besides health status, exogenous chemicals may greatly influence GST-mediated drug detoxication capacity of the liver. As observed for CYPs (5,11,12), we found that IL-1 decreased induction of some GST subunits by 3-methylcholanthrene (MC, a polycyclic aromatic hydrocarbon), phenobarbital (PB, a barbiturate), and oltipraz (OPZ, a synthetic derivative of 1,2-dithiole-3-thione).…”

mentioning

confidence: 51%

“…All these recombinant cytokines were known to be effective on CYP expression and/or acute-phase protein production in rat hepatocyte primary cultures (5,14). The cytokines and the three xenobiotic inducers (PB, MC, and OPZ) were added 24 h after cell seeding and at each daily renewal of the culture medium.…”

Section: Methodsmentioning

confidence: 99%

“…Hepatocytes were treated with ␣-amanitin (2 g/ml) in the absence or presence of 100 units/ml IL-1. Total RNA isolated from cells 0, 4,8,12,14,16,18,20,24, and 28 h following ␣-amanitin treatment were analyzed by Northern blot and hybridized with the rGSTM1 probe as described under "Experimental Procedures." rGSTM1 mRNA level was related to 18 S rRNA levels, and values are represented as the log of the untreated controls.…”

Section: Figmentioning

confidence: 99%

“…Several in vivo and in vitro studies have shown that administration of proinflammatory cytokines results in the decrease of hepatic drug metabolism and various cytochrome P-450 (CYP) 1 -related activities (4,5).…”

mentioning

confidence: 99%

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Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Mahéo¹,

Antras-Ferry

Morel

et al. 1997

Journal of Biological Chemistry

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The influence of various cytokines on the expression of glutathione S-transferases (GSTs) was investigated in rat hepatocytes in primary culture. Only treatment of hepatocytes with interleukin-1␤ (IL-1) was effective, resulting in a marked decrease in GSTs. Steady-state mRNA levels of rGSTA2 and M1 were strongly downregulated by IL-1 in a dose-dependent manner after a 24-h exposure while rGSTP1 mRNA level was increased by a 48-h treatment. Similar effects of IL-1 were observed at the protein level. The response to IL-1 appeared to be specific for each subunit within GST gene families. In addition, IL-1 strongly suppressed the induction of rGSTA2 by 3-methylcholanthrene, oltipraz (a synthetic derivative of 1,2-dithiole-3-thione), and phenobarbital and that of rGSTM1 by oltipraz and phenobarbital, whereas it was ineffective on rGSTP1 induction by these compounds. Using in vitro nuclear run-on transcription assay and Northern blot analysis of ␣-amanitin-treated cells, IL-1-mediated rGSTM1 mRNA decrease was found to result from mRNA destabilization. These results provide the first demonstration that IL-1 regulates some major GST subunits in hepatocytes by a post-transcriptional mechanism.

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mentioning

confidence: 51%

Section: Methodsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

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Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Mahéo¹,

Antras-Ferry

Morel

et al. 1997

Journal of Biological Chemistry

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“…Proinflammatory cytokines such as IL-1, IL-6, and TNF-a can suppress CYP expression in hepatocytes. [42][43][44][45] Indeed, intrahepatic CYP expression was depressed in inflammation and infection, where these proinflammatory cytokines are presumed to be produced abundantly. 32,46 Similarly, Liu et al 47 demonstrated that the pretreatment of LPS-sensitive C3H/OuJ mice but not LPS-resistant C3H/HeJ mice with a sublethal dose of LPS attenuated APAP hepatotoxicity by downregulating hepatic P450 enzymes in the livers.…”

Section: Il-1ra and Apap-induced Liver Injury T Ishibe Et Almentioning

confidence: 99%

Reduced acetaminophen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist

Ishibe

Kimura

Ishida

et al. 2009

Laboratory Investigation

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Acetaminophen (APAP) induced increases in intrahepatic expression of interleukin (IL)-1a, IL-1b, and IL-1 receptor antagonist (IL-1ra), when administered intraperitoneally. These observations prompted us to define the pathophysiological roles of IL-1ra in APAP-induced liver injury. Compared with wild-type (WT) mouse-derived hepatocytes, IL-1ra-deficient (IL-1ra KO)-derived hepatocytes exhibited more resistance against APAP but not APAP-derived major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Moreover, the amounts of a major APAP adduct (selenium-binding protein), an indicator of NAPQI generation from APAP, was significantly lower in IL-1ra KO mice than WT mice with depressed intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, the enzymes crucially involved in NAPQI generation from APAP. These observations would indicate that IL-1ra deficiency impaired APAP metabolism. IL-1a and IL-1b were expressed to similar extents in livers of untreated IL-1ra KO and WT mice. By contrast, the intranuclear amount of p65 of NF-kB, which can suppress the gene expression of CYP1A2, CYP2E1, and CYP3A11, was higher in untreated IL-1ra KO than WT mice. Moreover, when mice were intraperitoneally administered APAP (200 mg/kg), IL-1ra KO mice exhibited attenuated APAP-induced liver injury as evidenced by reductions in serum alanine transferase levels and histopathological changes such as centrilobular necrosis, hemorrhages, and leukocyte infiltration. Finally, when given 12 h before APAP challenge, IL-1a repressed the intrahepatic expression of CYP1A2, CYP2E1, and CYP3A11, eventually reducing APAP-induced liver injury, along with reduction in APAP adducts. Collectively, NF-kB was activated without any stimuli by the genetic disruption of IL-1ra, and suppressed cytochrome P450 enzyme expression, thereby reducing APAP-induced liver injury.

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Evaluating and Predicting Human Cytochrome P450 Enzyme Induction

Sinz

Kim

Ferguson³

et al. 2008

Drug Metabolism Handbook

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Interleukin‐1β antagonizes phenobarbital induction of several major cytochromes P450 in adult rat hepatocytes in primary culture

Cited by 60 publications

References 41 publications

Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Reduced acetaminophen-induced liver injury in mice by genetic disruption of IL-1 receptor antagonist

Evaluating and Predicting Human Cytochrome P450 Enzyme Induction

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