Dimethyl itaconate inhibits secondary wave of NF-?B signaling in macrophage activation

Natural metabolite itaconate and its membrane permeable derivative dimethyl itaconate (DI) selectively inhibit a subset of cytokines during macrophage activation (e.g. IL-1ß, IL-6, IL-12 but not TNF-a). Selectivity of DI action stems from the inhibitory effects of secondary, but not primary, wave of NF-?B signaling. Overall design: Bone marrow-derived macrophages (BMDMs) from C57BL/6 mice were stimulated with LPS + IFNg for indicated timepoints. Some samples were treated with dimethyl itaconate for 12h prior to LPS stimulation.