{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rzepecka J"],"funding":["Versus Arthritis","Medical Research Council","Diabetes UK","Wellcome Trust","Biotechnology and Biological Sciences Research Council"],"pagination":["59-73"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4459730"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["60"],"pubmed_abstract":["Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many patients are refractory to existing conventional and biologic therapies, and hence successful development of novel treatments remains a critical requirement. Towards this, we now describe a synthetic drug-like small molecule analogue, SMA-12b, of an immunomodulatory parasitic worm product, ES-62, which acts both prophylactically and therapeutically against collagen-induced arthritis (CIA) in mice. Mechanistic analysis revealed that SMA-12b modifies the expression of a number of inflammatory response genes, particularly those associated with the inflammasome in mouse bone marrow-derived macrophages and indeed IL-1β was the most down-regulated gene. Consistent with this, IL-1β was significantly reduced in the joints of mice with CIA treated with SMA-12b. SMA-12b also increased the expression of a number of genes associated with anti-oxidant responses that are controlled by the transcription factor NRF2 and critically, was unable to inhibit expression of IL-1β by macrophages derived from the bone marrow of NRF2(-/-) mice. Collectively, these data suggest that SMA-12b could provide the basis of an entirely novel approach to fulfilling the urgent need for new treatments for RA."],"journal":["Journal of autoimmunity"],"pubmed_title":["Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome."],"pmcid":["PMC4459730"],"funding_grant_id":["086852","12/0004458","E013929","18413","MC_PC_13063","BB/E013929/1"],"pubmed_authors":["Rzepecka J","Corbet M","Meakin PJ","Harnett MM","Lumb FE","Al-Riyami L","Khalaf AI","Huggan JK","Suckling CJ","Rodgers DT","Pineda MA","Harnett W","Ashford ML"],"additional_accession":[]},"is_claimable":false,"name":"Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome.","description":"Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many patients are refractory to existing conventional and biologic therapies, and hence successful development of novel treatments remains a critical requirement. Towards this, we now describe a synthetic drug-like small molecule analogue, SMA-12b, of an immunomodulatory parasitic worm product, ES-62, which acts both prophylactically and therapeutically against collagen-induced arthritis (CIA) in mice. Mechanistic analysis revealed that SMA-12b modifies the expression of a number of inflammatory response genes, particularly those associated with the inflammasome in mouse bone marrow-derived macrophages and indeed IL-1β was the most down-regulated gene. Consistent with this, IL-1β was significantly reduced in the joints of mice with CIA treated with SMA-12b. SMA-12b also increased the expression of a number of genes associated with anti-oxidant responses that are controlled by the transcription factor NRF2 and critically, was unable to inhibit expression of IL-1β by macrophages derived from the bone marrow of NRF2(-/-) mice. Collectively, these data suggest that SMA-12b could provide the basis of an entirely novel approach to fulfilling the urgent need for new treatments for RA.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Jun","modification":"2026-05-01T15:13:10.829Z","creation":"2019-03-27T01:53:03Z"},"accession":"S-EPMC4459730","cross_references":{"pubmed":["25975491"],"doi":["10.1016/j.jaut.2015.04.005"]}}