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• W2074636699 abstract "We previously reported that lead nitrate (LN), an inducer of hepatic tumor necrosis factor-α (TNF-α), downregulated gene expression of cholesterol 7α-hydroxylase. Herein, to clarify the role of TNF-α in LN-induced downregulation of cholesterol 7α-hydroxylase, effects of LN on gene expression of hepatic cholesterol 7α-hydroxylase (Cyp7a1) in TNF-α-knockout (KO) and TNF-α-wild-type (WT) mice were comparatively examined. Gene expression of hepatic Cyp7a1 in both WT and KO mice decreased to less than 5% of the corresponding controls at 6–12 h after treatment with LN (100 μmol/kg body weight, iv). Levels of hepatic TNF-α protein in either WT or KO mice were below the detection limit, although expression levels of the TNF-α gene markedly increased at 6 h in WT mice by LN treatment, but not in KO mice. In contrast, in both WT and KO mice, levels of hepatic IL-1β protein, which is known to be a suppressor of the cholesterol 7α-hydroxylase gene in hamsters, were significantly increased 3–6 h after LN treatment. Furthermore, LN-induced downregulation of the Cyp7a1 gene did not necessarily result from altered gene expression of hepatic transcription factors, including positive regulators (liver X receptor α, retinoid X receptor α, fetoprotein transcription factor, and hepatocyte nuclear factor 4α) and a negative regulator small heterodimer partner responsible for expression of the Cyp7a1 gene. The present findings indicated that LN-induced downregulation of the Cyp7a1 gene in mice did not necessarily occur through a TNF-α–dependent pathway and might occur mainly through an IL-1β–dependent pathway." @default.
• W2074636699 created "2016-06-24" @default.
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• W2074636699 date "2005-07-27" @default.
• W2074636699 modified "2023-10-16" @default.
• W2074636699 title "Tumor Necrosis Factor-α-Independent Downregulation of Hepatic Cholesterol 7α-Hydroxylase Gene in Mice Treated with Lead Nitrate" @default.
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• W2074636699 doi "https://doi.org/10.1093/toxsci/kfi267" @default.
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