Electrophilic Nrf2 activators and itaconate inhibit inflammation at low dose and promote IL-1β production and inflammatory apoptosis at high dose.

ABSTRACT: Controlling inflammation is critical for preventing many diseases including cancer, autoimmune disorders and hypersensitivity reactions. NF-E2-related factor 2 (Nrf2) is a key transcription factor that controls the cellular antioxidant and cytoprotective response. Moreover, Nrf2 has been implicated in the regulation of inflammatory processes, although the ultimate mechanism by which this is achieved is unknown. Here, we investigated mechanisms of inflammation and cell death pathways induced by a variety of Nrf2 activators including dimethyl fumarate (DMF) and the endogenous metabolite itaconate. We found that exposure of bone marrow-derived dendritic cells (BMDCs) to low concentrations of a variety of electrophilic Nrf2 activators including itaconate prior to Toll-like receptor (TLR) stimu

SUBMITTER: Muri J 

PROVIDER: S-EPMC7387846 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature