Activation of the transcription factor NRF2 mediates the anti-inflammatory properties of a subset of over-the-counter and prescription NSAIDs

Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

“…This work defines two previously unappreciated signalling axes linked to FH inhibition, uncovering its role in the regulation of IL-10, TNF and GDF15. Recent developments that have identified GDF15 as a mediator of immune tolerance, and the anti-inflammatory properties of colchicine and nonsteroidal anti-inflammatory drugs 37,38 , suggest that protective effects of DMF in models of inflammation could be mediated at least in part through GDF15. Moreover, increased TNF levels potentially explain adverse events reported with fumarate esters 39 .…”

Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis

“…Of note is that indomethacin, a NSAID used in rheumatic diseases for alleviating pain and inflammation [292], has been recently shown to behave like an electrophilic molecule that targets the Cys151 residue of KEAP1, inducing NRF2 activation and increased expression of some canonical NRF2 target genes (Nag-1/GDF15, CAT, GAR, GCLM, HMOX1, NQO1 and TALDO1) in primary human and mouse macrophages, independent of cyclooxygenase inhibition [268]. This study also demonstrated NRF2 target engagement by indomethacin in mice with endotoxemia and gout, but no human study has been so far performed to bring again into focus indomethacin for controlling pain, inflammation and redox disturbances in RA.…”

Immune sensing of food allergens promotes aversive behaviour

“…4 a, b). Thus, we sought to directly test whether GDF15 was necessary for the aversive response to OVA using anti-GDF15 neutralizing antibody 60 . We sensitized WT mice with OVA/alum and treated them 5 h prior to each day of OVA preference testing with isotype control or anti-GDF15 antibody (Extended Data Fig.…”