Dimethyl itaconate inhibits TNF-α induced NF-κB signaling pathway in human epithelial cells

Abstract

Background: Dimethyl itaconate (DMI), a membrane-permeable derivative of itaconate, was found to moderate IL-17-IκBζ-induced skin pathology including psoriasis in mouse experiments. TNF-α induced NF-κB pathway, which controls a variety of immune and inflammatory responses, was also proven to play a crucial role as mediator in psoriasis. However, whether DMI interacts with the TNF-α induced NF-κB pathway remains unclear.Results: Here we show that DMI inhibits TNF-α induced NF-κB transcriptional activities in dosedependent manner in several human cell lines using dual luciferase assay and blocks the NF-κB nuclear entry. Moreover, DMI potently inhibits IKKβ dependent phosphorylation and degradation of