RT Journal Article
SR Electronic
T1 4-Octyl-Itaconate and Dimethyl Fumarate Inhibit COX2 Expression and Prostaglandin Production in Macrophages
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 2561
OP 2569
DO 10.4049/jimmunol.2100488
VO 207
IS 10
A1 Diskin, Ciana
A1 Zotta, Alessia
A1 Corcoran, Sarah E.
A1 Tyrrell, Victoria J.
A1 Zaslona, Zbigniew
A1 O’Donnell, Valerie B.
A1 O’Neill, Luke A. J.
YR 2021
UL http://www.jimmunol.org/content/207/10/2561.abstract
AB 4-OI reduces COX2 expression and inhibits PG production in macrophages.DMF also attenuates COX2 expression in macrophages and decreases PGs.The 4-OI– and DMF-induced decrease in COX2 and PGs is NRF2 independent.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.This article is featured in Top Reads, p.