The Anti-Inflammatory Activity of Ferulic Acid on NF- ?BDepends on Keap1

Nrf2 and NF-?B are the two master transcriptional factors activated by different cellular signals turned to counteract the deleterious effects of pathological cellular processes linked to inflammation and oxidative stress.Several recent studies have highlighted a molecular connection between NF-?B and Keap1/Nrf2 pathways. The Keap1 protein seems to be the central player in this interaction, as it is involved in both IKK?-NF-?B and Nrf2 modulation. Ferulic acid (FA) is a well-known antioxidant and antiinflammatory agent, able to relieveinflammatory response viaNF-?B/IKK kinase, but until now the complete molecular network under its action is not all clear. Immunoblot data conducted on LPS-treated macrophage-like RAW264.7 cells transfected with si- Keap1 show that the FA anti-inflammatory and modulatory effects on NF-?B are abolished. Luciferase assay conducted in human A549 cell line, in which Keap1 protein is partially inactive, highlights that NF-?B activation induced by LPS is refractory to FA inhibition. This study proved that Keap1 and IKK together are important modulators of NF-?B and their activity is essential for FA anti-inflammatory effectiveness