Skip to main content
. Author manuscript; available in PMC: 2020 May 1.
Published in final edited form as: J Immunol. 2019 Mar 18;202(9):2737–2746. doi: 10.4049/jimmunol.1801627

Figure 2. Inhibition of IFN-α production by DMF occurs through multiple TLR signaling pathways and is mostly independent of NRF2 or GSH abundance.

Figure 2.

(A) DMF inhibits TLR7 and TLR9-induced pDC IFN-α production. pDCs were isolated from human blood and treated with 50μM DMF for 18 h along with 1 μM CpG-A, 1 μM CpG-B, one multiplicity of infection with Influenza virus, 100nM R-848 or 500uM Loxoribine and the levels of IFN-α were quantified by ELISA. Results are representative of at least two independent experiments and *** P < 0.005, **** P < 0.0001 by two-tailed unpaired t test. (B) Structures of dimethyl fumarate (DMF) analogs. DEF: diethyl fumarate; DMM: dimethyl maleate; DEM: diethyl maleate; DiPrF: diisopropyl fumarate; DBnF: dibenzyl fumarate; DMenF: dimenthyl fumarate; TMA: tetramethyl fumaramide; DMS: dimethyl succinate; MMF: monomethyl fumarate. (C) IFN-α release from purified human pDCs stimulated with CpG-A and treated concomitantly with 50 μM of indicated compounds in (B) for 18 h. (D) IFN-α release measured by ELISA from purified human pDCs stimulated with CpG-A and treated with either the NRF2 inhibitor ML385 (5 μM), DMF (50 μM), or ML385 and DMF. (E) IFN-α release measured by ELISA from purified human pDCs stimulated with CpG-A and treated with either the glutathione inhibitor BSO (2 mM), DMF (50 μM), or BSO and DMF. Results are representative of at least two independent experiments and *** P < 0.005 by two-tailed unpaired t test.