@article {Bell205, author = {Jordan C. Bell and Henry W. Strobel}, title = {Regulation of Cytochrome P450 4F11 by Nuclear Transcription Factor-κB}, volume = {40}, number = {1}, pages = {205--211}, year = {2012}, doi = {10.1124/dmd.111.041178}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Although the mechanisms that regulate CYP4F genes have been and are currently being studied in a number of laboratories, the specific mechanisms for the regulation of these genes are not yet fully understood. This study shows that nuclear factor κB of the light-chain-enhancer in activated B cells (NF-κB) can inhibit CYP4F11 expression in human liver carcinoma cell line (HepG2) as summarized below. Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, has been shown to activate NF-κB signaling while also activating the c-Jun NH2-terminal kinase (JNK) signaling pathway. Other studies have reported that JNK signaling can up-regulate CYP4F11 expression. The results of this study demonstrate that in the presence of TNF-α and the specific NF-κB translocation inhibitor N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (IMD-0354), there is a greater increase in CYP4F11 expression than that elicited by TNF-α alone, indicating that NF-κB plays an inhibitory role. Moreover, NF-κB stimulation by overexpression of mitogen-activated protein kinase kinase kinase inhibited CYP4F11 promoter expression. CYP4F11 promoter inhibition can also be rescued in the presence of TNF-α when p65, a NF-κB protein, is knocked down. Thus, NF-κB signaling pathways negatively regulate the CYP4F11 gene.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/40/1/205}, eprint = {https://dmd.aspetjournals.org/content/40/1/205.full.pdf}, journal = {Drug Metabolism and Disposition} }