Anti-inflammatory Effect of a Cell-Penetrating Peptide Targeting the Nrf2/Keap1 Interaction

• Published in: ACS medicinal chemistry letters Vol. 3; no. 5; pp. 407 - 410
• Main Authors: Steel, Richard, Cowan, Jonathan, Payerne, Estelle, O'Connell, Maria A, Searcey, Mark
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.05.2012
• Subjects: Letter; Nrf2; Keap-1; inflammation; cell-penetrating peptide; protein−protein interaction; antioxidant response
• ISSN: 1948-5875; 1948-5875
• DOI: 10.1021/ml300041g

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.