Pretranslational down-regulation of cytochromes P450 2C11 and 3A2 in male rat liver by tumor necrosis factor α

Nadin, Louise; Butler, Alison; Farrell, Geoffrey C.; Murray, Michael T.

doi:10.1016/0016-5085(95)90285-6

Cited by 52 publications

(20 citation statements)

References 27 publications

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“…Up-regulation of CYP7B activity by TNF␣ and IL-1␤ has also been observed in rat ovarian cells (34). Interestingly, TNF␣ has been found to down-regulate other P450 enzymes, such as CYP7A, CYP2C11, and CYP3A2 expressed in the liver and hepatocytes and CYP1A1 expressed in adipose tissue stromal cells (35)(36)(37)(38). In this study, we found that the anti-TNFRI antibody by itself increased CYP7B activity.…”

Section: Discussionsupporting

confidence: 53%

CYP7B expression and activity in fibroblast‐like synoviocytes from patients with rheumatoid arthritis: Regulation by proinflammatory cytokines

Dulos¹,

Vleuten²,

Kavelaars³

et al. 2005

Arthritis & Rheumatism

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Objective. The cytochrome P450 enzyme CYP7B catalyzes the conversion of dehydroepiandrosterone (DHEA) into 7␣-hydroxy-DHEA (7␣-OH-DHEA). This metabolite can stimulate the immune response. We previously reported that the severity of murine collageninduced arthritis is correlated with CYP7B messenger RNA (mRNA) expression and activity in the arthritic joint. The purpose of this study was to investigate the presence of 7␣-OH-DHEA in synovial samples and the cytokine regulation of CYP7B activity in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods. The presence of 7␣-OH-DHEA was examined in synovial biopsy tissues, synovial fluid, and serum by radioimmunoassay. The effect of cytokines on CYP7B mRNA expression and CYP7B activity in FLS was examined by determining the formation of the CYP7B enzyme product 7␣-OH-DHEA with the use of high-performance liquid chromatography.Results. The CYP7B enzyme product 7␣-OH-DHEA was found in synovial biopsy tissues, synovial fluid, and serum from RA patients. The proinflammatory cytokines tumor necrosis factor ␣ (TNF␣), interleukin-1␣ (IL-1␣), IL-1␤, and IL-17 up-regulated CYP7B activity in an FLS cell line 2-10-fold. Enhanced CYP7B activity was correlated with an increase in CYP7B mRNA. The cytokine transforming growth factor ␤ inhibited CYP7B activity. Moreover, CYP7B activity was detected in 10 of 13 unstimulated synovial fibroblast cell lines. Stimulation with TNF␣ increased CYP7B activity in all cell lines tested.Conclusion. Exposure to the proinflammatory cytokines TNF␣, IL-1␣, IL-1␤, and IL-17 increases CYP7B activity in synovial tissue. Increased CYP7B activity leads to higher levels of the DHEA metabolite 7␣-OH-DHEA in synovial fluid, which may contribute to the maintenance of the chronic inflammation observed in RA patients.

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Section: Discussionsupporting

confidence: 53%

CYP7B expression and activity in fibroblast‐like synoviocytes from patients with rheumatoid arthritis: Regulation by proinflammatory cytokines

Dulos¹,

Vleuten²,

Kavelaars³

et al. 2005

Arthritis & Rheumatism

View full text Add to dashboard Cite

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“…CYP1A2 is the most predominant CYP isoform in the rat liver, and CYP2C11 is down-regulated by TNF-␣ in the rat liver at the pretranslational level [25]. In our study, the gene expression of both CYP isoforms have already been downregulated 20 h after hemorrhagic shock.…”

Section: Discussionmentioning

confidence: 86%

Downregulation of Hepatic Cytochrome P-450 Isoforms and PPAR-γ: Their Role in Hepatic Injury and Proinflammatory Responses in a Double-Hit Model of Hemorrhage and Sepsis

Higuchi

Zhou

et al. 2007

Journal of Surgical Research

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“…In fact, TNF and other proinflammatory cytokines have been shown to downregulate CYPs. 38,[58][59][60] Three lines of evidence, however, strongly suggest that the rate and extent of APAP bioactivation were similar in wild-type and TNF/LT-␣-deficient mice. First, the microsomal activity of the major CYP form (CYP2E1) that catalyzes the formation of NAPQI and that of CYP1A2 were unaltered in the knockout mice.…”

Section: Discussionmentioning

confidence: 99%

Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-α gene knockout mice

et al. 1998

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Recent evidence suggests that macrophages and/or other nonparenchymal cells may release important mediators contributing to the hepatic necrosis induced by high doses of acetaminophen (APAP). The nature and causative role of these mediators has remained elusive, however. To investigate the role of the proinflammatory cytokine, tumor necrosis factor (TNF) in the initiation and early propagation of APAP-induced liver injury, we have used mice deficient in both TNF and the closely related lymphotoxin-␣ (LT-␣). Male TNF/LT-␣ knockout mice and C57BL/6 wild-type mice were treated with a hepatotoxic dose of APAP (400 mg/kg, intraperitoneally), and the development of liver injury was monitored over 8 hours. Both genotypes exhibited similar basal activities of hepatic cytochrome P450 2E1 and 1A2. After APAP administration, both the rate of glutathione consumption and the extent of subsequent selective protein binding did not differ significantly in the knockout and wild-type mice. The TNF/LT-␣-deficient mice developed severe centrilobular necrosis and exhibited highly increased levels of serum alanine aminotransferase and aspartate aminotransferase, the extent of which was not significantly different from that in wild-type mice. In C57BL/6 mice exposed to APAP, no increases in hepatic transcripts of TNF or LT-␣ were found by reverse transcription-polymerase chain reaction, nor was immunoreactive serum TNF detected by enzyme-linked immunosorbent assay over 8 hours posttreatment. These data indicate that, in the absence of the genes encoding for TNF and LT-␣, APAP bioactivation was not altered and mice still developed severe hepatic necrosis. Thus, TNF is unlikely to be a key mediator in the early pathogenesis of APAP-induced hepatotoxicity. (HEPATOLOGY 1998;27:1021-1029.)

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Pretranslational down-regulation of cytochromes P450 2C11 and 3A2 in male rat liver by tumor necrosis factor α

Cited by 52 publications

References 27 publications

CYP7B expression and activity in fibroblast‐like synoviocytes from patients with rheumatoid arthritis: Regulation by proinflammatory cytokines

CYP7B expression and activity in fibroblast‐like synoviocytes from patients with rheumatoid arthritis: Regulation by proinflammatory cytokines

Downregulation of Hepatic Cytochrome P-450 Isoforms and PPAR-γ: Their Role in Hepatic Injury and Proinflammatory Responses in a Double-Hit Model of Hemorrhage and Sepsis

Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-α gene knockout mice

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