biostudies-literatureDiskin CEuropean Research CouncilScience Foundation IrelandEC | European Regional Development FundWellcome Trust2561-2569https://www.ebi.ac.uk/biostudies/studies/S-EPMC7613254biostudies-literatureUnknown207(10)PGs are important proinflammatory lipid mediators, the significance of which is highlighted by the widespread and efficacious use of nonsteroidal anti-inflammatory drugs in the treatment of inflammation. 4-Octyl itaconate (4-OI), a derivative of the Krebs cycle-derived metabolite itaconate, has recently garnered much interest as an anti-inflammatory agent. In this article, we show that 4-OI limits PG production in murine macrophages stimulated with the TLR1/2 ligand Pam3CSK4. This decrease in PG secretion is due to a robust suppression of cyclooxygenase 2 (COX2) expression by 4-OI, with both mRNA and protein levels decreased. Dimethyl fumarate, a fumarate derivative used in the treatment of multiple sclerosis, with properties similar to itaconate, replicated the phenotype observed with 4-OJournal of immunology (Baltimore, Md. : 1950)4-Octyl-Itaconate and Dimethyl Fumarate Inhibit COX2 Expression and Prostaglandin Production in Macrophages.PMC7613254205455834370109443109443/Z/15/Z12/IA/ 1531O'Neill LAJCorcoran SEZaslona ZDiskin CO'Donnell VBZotta ATyrrell VJfalse4-Octyl-Itaconate and Dimethyl Fumarate Inhibit COX2 Expression and Prostaglandin Production in Macrophages.PGs are important proinflammatory lipid mediators, the significance of which is highlighted by the widespread and efficacious use of nonsteroidal anti-inflammatory drugs in the treatment of inflammation. 4-Octyl itaconate (4-OI), a derivative of the Krebs cycle-derived metabolite itaconate, has recently garnered much interest as an anti-inflammatory agent. In this article, we show that 4-OI limits PG production in murine macrophages stimulated with the TLR1/2 ligand Pam3CSK4. This decrease in PG secretion is due to a robust suppression of cyclooxygenase 2 (COX2) expression by 4-OI, with both mRNA and protein levels decreased. Dimethyl fumarate, a fumarate derivative used in the treatment of multiple sclerosis, with properties similar to itaconate, replicated the phenotype observed with 4-O2021-01-01T00:00:00Z2021 Nov2025-04-04T02:26:28.53Z2025-02-19T02:27:01.614ZS-EPMC76132543463558510.4049/jimmunol.2100488