Effect of interleukin-6 neutralization on CYP3A11 and metallothionein-1/2 expressions in arthritic mouse liver

Ashino, Takashi; Arima, Yoshiko; Shioda, Seiji; Iwakura, Yoichiro; Numazawa, Satoshi; Yoshida, Takemi

doi:10.1016/j.ejphar.2006.11.072

Cited by 37 publications

(34 citation statements)

References 30 publications

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“…For this purpose, we assessed testosterone 6β-hydroxylase activity and the CL int of nifedipine, which are well-known assays of CYP3A enzyme activity. 30) Table 2 shows the effects of LPS on 6β-hydroxylase activity and the hepatic CL int of nifedipine under the conditions of PCN treatment alone or PCN plus LPS. The PCN-only condition induced about a 3-fold increase in 6β-hydroxylase activity compared to controls.…”

Section: Fig 3 Effect Of Lps On the Expression Of Cyp1a2 Mrna In B(mentioning

confidence: 99%

“…The organic layer was isolated, and the solvent was evaporated under a nitrogen gas stream. The residue was dissolved in 150 µL of solvent A, consisting of methanol, acetonitrile, and H 2 O (39 : 60 : 1, v/v/v), injected into the HPLC apparatus, and analyzed as previously described by Ashino et al 30) The HPLC system consisted of a model L-2130 liquid chromatograph pump, a model L-2455 diode array detector, a model L-2200 auto sampler, a model L-column oven (all from Hitachi High Technologies Co., Tokyo, Japan), and a 4.6×150 mm COSMOSIL 5C 18 -MS-II packed column (Nacalai Tesque). The mobile phase consisted of solvent A and methanol, acetonitrile, and H 2 O (80 : 18 : 2, v/v/v; solvent B).…”

Section: )mentioning

confidence: 99%

“…29,30) Testosterone 6β-hydroxylation was assayed as follows. The reaction mixture (0.5 mL, containing 0.5 mg/mL microsomal protein, 1.3 mM β-NADP + , 3.3 mM glucose 6-phosphate, 0.4 U/ mL glucose 6-phosphate dehydrogenase, 3.3 mM magnesium chloride, and 50 µM testosterone in 100 mM sodium phosphate buffer (pH 7.4)) was incubated at 37°C for 15 min, and the reaction was stopped by adding tert-butyl methyl ether.…”

Section: )mentioning

confidence: 99%

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Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Moriya

Kataoka

Fujino

et al. 2012

Biological & Pharmaceutical Bulletin

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Infection-associated inflammation can alter the expression levels and functions of cytochrome P450s (CYPs). Cyp gene expression is regulated by the activation of several nuclear receptors, including pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR). These receptors can be activated by xenobiotics, including medicines. Here, to study the xenobiotic-induced fluctuations in CYP during inflammation, we examined the effect of lipopolysaccharide (LPS) treatment on the level of mRNAs encoding hepatic CYPs induced by xenobiotic-activated nuclear receptors, in mice. Both the mRNA induction of Cyp genes and the metabolic activities of CYP proteins were examined. LPS treatment caused a significant decrease in the induced expression of the mRNAs for Cyp3a11, 2c29, 2c55, and 1a2, but not for Cyp2b10. To assess the CYP enzymatic activities, CYP3A-mediated testosterone 6β-hydroxylation and the intrinsic clearance (CL int ) of nifedipine in liver microsomes were measured in mice treated with the xenobiotic pregnenolone-16alpha-carbonitrile (PCN) with or without LPS administration. Both assays revealed that the CYP3A activity, which was induced by PCN, declined significantly after LPS treatment, and this decline correlated with the Cyp3a11 mRNA level. In addition, we found that the mRNAs for interleukin (IL)-1β and tumor necrosis factor (TNF) α were increased after treatment with LPS plus xenobiotics. Our findings demonstrated that LPS treatment reduces the PXR-and AhR-mediated, and possibly CAR-mediated Cyp gene expression and further suggest that these decreases are dependent on inflammatory cytokines in the liver.

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Section: Fig 3 Effect Of Lps On the Expression Of Cyp1a2 Mrna In B(mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

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Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Moriya

Kataoka

Fujino

et al. 2012

Biological & Pharmaceutical Bulletin

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“…Hepatic Cyp1a and Cyp3a protein expression were decreased in rats with AA, and infliximab treatment increased Cyp1a and Cyp3a protein expression. Ashino et al (2007) used a murine anti-IL-6 monoclonal antibody to treat arthritis in a Human T-Cell Lymphotropic Virus type 1 (HTLV-1) transgenic mouse arthritis model. IL-6 was significantly increased in the arthritic mice, and Cyp3a protein was 60% of nonarthritic transgenic controls.…”

Section: Preclinical Approaches To Cytokine-mediated Tp-ddi Evaluationmentioning

confidence: 99%

Critical Review of Preclinical Approaches to Investigate Cytochrome P450–Mediated Therapeutic Protein Drug-Drug Interactions and Recommendations for Best Practices: A White Paper

et al. 2013

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“…While many preclinical CYP suppression studies have used lipopolysaccharide (LPS) endotoxin to induce an acute phase response in vivo (10), there are few studies on the ablation of CYP suppression by rodent-specific anti-cytokine antibodies in rodent models of inflammatory disease (11)(12)(13). One common feature which links preclinical in vivo LPS-mediated CYP suppression studies and clinical disease treatment effects on CYP3A is that the upper limit of CYP activity changes is generally about 2-3-fold.…”

Section: In Vivo Challengesmentioning

confidence: 99%

Therapeutic Protein Drug–Drug Interactions: Navigating the Knowledge Gaps–Highlights from the 2012 AAPS NBC Roundtable and IQ Consortium/FDA Workshop

Kenny¹,

Liu²,

Chow

et al. 2013

AAPS J

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Abstract. The investigation of therapeutic protein drug-drug interactions has proven to be challenging. In May 2012, a roundtable was held at the American Association of Pharmaceutical Scientists National Biotechnology Conference to discuss the challenges of preclinical assessment and in vitro to in vivo extrapolation of these interactions. Several weeks later, a 2-day workshop co-sponsored by the U.S. Food and Drug Administration and the International Consortium for Innovation and Quality in Pharmaceutical Development was held to facilitate better understanding of the current science, investigative approaches and knowledge gaps in this field. Both meetings focused primarily on drug interactions involving therapeutic proteins that are pro-inflammatory cytokines or cytokine modulators. In this meeting synopsis, we provide highlights from both meetings and summarize observations and recommendations that were developed to reflect the current state of the art thinking, including a four-step risk assessment that could be used to determine the need (or not) for a dedicated clinical pharmacokinetic interaction study.

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Effect of interleukin-6 neutralization on CYP3A11 and metallothionein-1/2 expressions in arthritic mouse liver

Cited by 37 publications

References 30 publications

Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Effect of Lipopolysaccharide on the Xenobiotic-Induced Expression and Activity of Hepatic Cytochrome P450 in Mice

Critical Review of Preclinical Approaches to Investigate Cytochrome P450–Mediated Therapeutic Protein Drug-Drug Interactions and Recommendations for Best Practices: A White Paper

Therapeutic Protein Drug–Drug Interactions: Navigating the Knowledge Gaps–Highlights from the 2012 AAPS NBC Roundtable and IQ Consortium/FDA Workshop

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