Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response.

Authors: Sun, Kaitlyn A; Li, Yan; Meliton, Angelo Y; Woods, Parker S; Kimmig, Lucas M; Cetin-Atalay, Rengül; Hamanaka, Robert B; Mutlu, Gökhan M

Published In Elife, (2020 04 07)

Abstract: Particulate matter (PM) air pollution causes cardiopulmonary mortality via macrophage-driven lung inflammation; however, the mechanisms are incompletely understood. RNA-sequencing demonstrated Acod1 (Aconitate decarboxylase 1) as one of the top genes induced by PM in macrophages. Acod1 encodes a mitochondrial enzyme that produces itaconate, which has been shown to exert anti-inflammatory effects via NRF2 after LPS. Here, we demonstrate that PM induces Acod1 and itaconate, which reduced mitochondrial respiration via complex II inhibition. Using Acod1-/- mice, we found that Acod1/endogenous itaconate does not affect PM-induced inflammation or NRF2 activation in macrophages in vitro or in vivo. In contrast, exogenous cell permeable itaconate, 4-octyl itaconate (OI) attenuated PM-induced inflammation in macrophages. OI was sufficient to activate NRF2 in macrophages; however, NRF2 was not required for the anti-inflammatory effects of OI. We conclude that the effects of itaconate production on inflammation are stimulus-dependent, and that there are important differences between endogenous and exogenously-applied itaconate.

PubMed ID: 32255424 Exiting the NIEHS site

MeSH Terms: Animals; Carboxy-Lyases/genetics*; Inflammation*; Macrophages, Alveolar/drug effects; Macrophages, Alveolar/metabolism*; Mice; Mice, Knockout; NF-E2-Related Factor 2/genetics*; Oxygen/metabolism; Particulate Matter/administration & dosage*; RNA-Seq; Signal Transduction; Succinates/metabolism*; Succinates/pharmacology

Back
to Top