title: Anti-inflammatory Effect of a Cell-Penetrating Peptide Targeting the Nrf2/Keap1 Interaction.
abstract: Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is increasingly recognized as a central regulator of multiple signaling pathways in inflammation and cancer, and the ability to use chemical biological tools to investigate its biological effects is very attractive. A peptide comprising a TAT-conjugated Nrf2 sequence is shown to activate Nrf2 and its downstream target gene heme-oxygenase-1 (HO-1) in a dose-dependent manner in intact human THP-1 monocytes. Levels of Nrf2 protein peak after 3 h, whereas HO-1 mRNA and protein peak after 6 and 12 h, respectively. The peptide is also shown to inhibit the production of the pro-inflammatory cytokine TNF. The TAT-14mer constitutes a useful chemical biology tool with potential therapeutic applications.
authors.affiliation: School of Pharmacy,  University of East Anglia , Norwich NR4 7TJ, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Steel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cowan
authors.forename: Estelle
authors.initials: E
authors.lastname: Payerne
authors.forename: Maria A
authors.initials: MA
authors.lastname: O'Connell
authors.forename: Mark
authors.initials: M
authors.lastname: Searcey