Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
The nuclear receptor pregnane X receptor (PXR) is a xenobiotic-responsive transcription factor that is highly expressed in the liver and intestine. PXR is activated by various chemicals and plays a pivotal role in the expression of drug-metabolizing enzymes. Recent studies have revealed that PXR also plays a role in the regulation of immune/inflammatory responses. Specific PXR activators, including synthetic ligands and phytochemicals, have been shown to ameliorate chemically induced colitis and/or liver injury in mice. Ligand-dependent PXR activation in hepatic stellate cells prevents its activation and thus liver steatosis in mice. PXR activation is also reported to prevent liver cancer promotion in chemical hepatocarcinogenesis model mice. Mechanistic analyses have suggested that the PXR-mediated preventing effects might be caused by an inhibition of the transcriptional activity of NF-κB, AP-1, and other transcription factors through protein-protein interactions. On the other hand, it is also reported that treatment with proinflammatory cytokines reduces the expression of PXR-target genes such as CYP3A in vivo and in vitro. These results strongly suggest that PXR and immune/inflammatory signals involving NF-kB and/or AP-1 mutually repress each other. In this symposium, we will introduce the regulatory roles of PXR in inflammatory signals and immune systems.
