Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1

We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.

Source: Nature - March 28, 2018 Category: Research Authors: Evanna L. Mills Dylan G. Ryan Hiran A. Prag Dina Dikovskaya Deepthi Menon Zbigniew Zaslona Mark P. Jedrychowski Ana S. H. Costa Maureen Higgins Emily Hams John Szpyt Marah C. Runtsch Martin S. King Joanna F. McGouran Roman Fischer Benedikt M. Kessler Anne Tags: Letter Source Type: research