Regulation of gene expression of hepatic drug metabolizing enzymes and transporters by the Toll-like receptor 2 ligand, lipoteichoic acid.
Regulation of gene expression of hepatic drug metabolizing enzymes and transporters by the Toll-like receptor 2 ligand, lipoteichoic acid.
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DOI：
10.1016/j.abb.2008.10.003
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发表时间：
2009-01-01
影响因子：
3.9
通讯作者：
Haque, Nadia
中科院分区：
文献类型：
--
作者：
Ghose, Romi;Guo, Tao;Haque, Nadia
关键词：
肝脏药物代谢酶 (DME) 的表达在感染和炎症中发生改变。然而，Gram+ve 细菌成分及其受体 Toll 样受体 (TLR) 2 在肝脏 DME 调节中的作用尚不清楚。 DME 的基因表达受核受体超家族成员（PXR、CAR 和 RXRα）的调节。 TLR2 配体脂磷壁酸 (LTA) 降低了小鼠肝脏中 CAR 及其靶基因 Cyp2b10、Cyp2a4 和 Sultn 的 RNA 水平（降低约 60-80%）。 LTA 适度降低了 PXR 和 CAR 调节的肝脏基因、Cyp3a11 和 Mrp2，同时 PXR RNA 和 RXRα 核蛋白水平降低了约 50%。用库普弗细胞抑制剂氯化钆预处理后，LTA 的作用显着减弱，表明库普弗细胞有助于 LTA 介导的肝基因下调。这些结果表明，用革兰氏+ve细菌成分治疗优先下调肝脏中的CAR及其靶基因。
Expression of hepatic drug metabolizing enzymes (DMEs) is altered in infection and inflammation. However, the role of Gram+ve bacterial components and their receptor, Toll-like receptor (TLR) 2 in regulation of hepatic DMEs is unknown. Gene expression of DMEs is regulated by members of the nuclear receptor superfamily (PXR, CAR and RXRα). The TLR2 ligand, lipoteichoic acid (LTA) reduced RNA levels of CAR and its target genes, Cyp2b10, Cyp2a4 and Sultn in mouse liver (~60-80% reduction). Hepatic genes regulated by PXR and CAR, Cyp3a11 and Mrp2 were moderately reduced by LTA, along with ~50% reduction of PXR RNA and nuclear protein levels of RXRα. The effects of LTA were significantly attenuated by pre-treatment with the Kupffer cell inhibitor, gadolinium chloride, indicating that Kupffer cells contribute to LTA-mediated down-regulation of hepatic genes. These results indicate that treatment with Gram+ve bacterial components preferentially down-regulate CAR and its target genes in the liver.
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影响因子：
3.9
作者：
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