Diskin, Ciana, Zotta, Alessia, Corcoran, Sarah E., Tyrrell, Victoria J., Zaslona, Zbigniew, O'Donnell, Valerie B. ![]() |
Abstract
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-OI. We also demonstrate that the decrease in COX2 expression and inhibition of downstream PG production occurs in an NRF2-independent manner. Our findings provide a new insight into the potential of 4-OI as an anti-inflammatory agent and also identifies a novel anti-inflammatory function of dimethyl fumarate.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Publisher: | American Association of Immunologists |
ISSN: | 0022-1767 |
Date of First Compliant Deposit: | 5 January 2023 |
Date of Acceptance: | 10 September 2021 |
Last Modified: | 31 Jan 2025 22:19 |
URI: | https://orca.cardiff.ac.uk/id/eprint/149102 |
Citation Data
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