Regulation of gene expression of hepatic drug metabolizing enzymes and transporters by the Toll-like receptor 2 ligand, lipoteichoic acid.

摘要: Abstract Expression of hepatic drug metabolizing enzymes (DMEs) is altered in infection and inflammation. However, the role Gram+ve bacterial components their receptor, Toll-like receptor (TLR) 2 regulation DMEs unknown. Gene expression regulated by members nuclear superfamily (PXR, CAR RXRα). The TLR2 ligand, lipoteichoic acid (LTA) reduced RNA levels its target genes, Cyp2b10, Cyp2a4 Sultn mouse liver (∼60–80% reduction). Hepatic genes PXR CAR, Cyp3a11 Mrp2 were moderately LTA, along with ∼50% reduction protein RXRα. effects LTA significantly attenuated pre-treatment Kupffer cell inhibitor, gadolinium chloride, indicating that cells contribute to LTA-mediated down-regulation genes. These results indicate treatment preferentially down-regulate liver.