Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages.

Nature Metabolism
Amanda SwainMaxim N Artyomov

Abstract

Following activation, macrophages undergo extensive metabolic rewiring1,2. Production of itaconate through the inducible enzyme IRG1 is a key hallmark of this process3. Itaconate inhibits succinate dehydrogenase4,5, has electrophilic properties6 and is associated with a change in cytokine production4. Here, we compare the metabolic, electrophilic and immunologic profiles of macrophages treated with unmodified itaconate and a panel of commonly used itaconate derivatives to examine its role. Using wild-type and Irg1-/- macrophages, we show that neither dimethyl itaconate, 4-octyl itaconate nor 4-monoethyl itaconate are converted to intracellular itaconate, while exogenous itaconic acid readily enters macrophages. We find that only dimethyl itaconate and 4-octyl itaconate induce a strong electrophilic stress response, in contrast to itaconate and 4-monoethyl itaconate. This correlates with their immunosuppressive phenotype: dimethyl itaconate and 4-octyl itaconate inhibited IκBζ and pro-interleukin (IL)-1β induction, as well as IL-6, IL-10 and interferon-β secretion, in an NRF2-independent manner. In contrast, itaconate treatment suppressed IL-1β secretion but not pro-IL-1β levels and, surprisingly, strongly enhanced lipopolysacch...Continue Reading

References

Oct 1, 1949·Proceedings of the Society for Experimental Biology and Medicine·W W ACKERMANN, V R POTTER
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Feb 28, 2007·Molecular and Cellular Biology·Elaine D MacKenzieEyal Gottlieb
Nov 6, 2010·Analytical Chemistry·Eugene MelamudJoshua D Rabinowitz
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Apr 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Alessandro MichelucciKarsten Hiller
May 18, 2016·The Journal of Biological Chemistry·Thekla CordesChristian M Metallo
Oct 30, 2016·Metabolic Engineering·Björn-Johannes HarderSteffen Klamt
Feb 12, 2017·The Journal of Biological Chemistry·Mahmoud ElAzzounyCharles F Burant
Oct 24, 2017·Cell·Hongying ShenVamsi K Mootha
Feb 2, 2019·Nature Reviews. Immunology·Luke A J O'Neill, Maxim N Artyomov

❮ Previous
Next ❯

Citations

Oct 30, 2020·Metabolites·Erika M PalmieriDaniel W McVicar
Oct 29, 2020·Current Opinion in Biotechnology·Yanling ZhangChu Wang
Oct 29, 2020·Current Opinion in Biotechnology·Jacob Thyrsted, Christian Kanstrup Holm
Dec 10, 2020·Current Opinion in Biotechnology·Thekla Cordes, Christian M Metallo
Jan 16, 2021·Scientific Reports·Claudia NastasiAnders Woetmann
Feb 13, 2021·Clinics and Research in Hepatology and Gastroenterology·Hong-Gang WangXiao-Zhong Yang
Feb 21, 2021·Current Opinion in Biotechnology·Wei HeKarsten Hiller
Feb 23, 2021·ELife·Rabina MainaliMatthew A Quinn
Mar 11, 2021·Cell Reports·Monika BambouskovaMaxim N Artyomov
Mar 11, 2021·Cell Reports·Natasha Lopes FischerIgor E Brodsky
Mar 9, 2021·Frontiers in Immunology·Julia Blay-CadanetChristian Kanstrup Holm
Apr 4, 2021·Metabolites·Evelyn RamplerGunda Koellensperger
Feb 2, 2021·Endocrine Reviews·Adil Rasheed, Katey J Rayner
May 18, 2021·Chemical Science·Yanling ZhangChu Wang
Apr 30, 2021·The Journal of Clinical Investigation·Rashi SinghalYatrik M Shah
Jul 10, 2021·Immunotherapy Advances·Shane M O'Carroll, Luke A J O'Neill
Aug 6, 2021·Frontiers in Cellular and Infection Microbiology·Amy A O'CallaghanSinéad C Corr
Jul 31, 2021·EMBO Reports·Gioacchino NatoliSerena Ghisletti
Aug 14, 2021·Nature Communications·Seth J ParkerAlec C Kimmelman
Aug 14, 2021·Cell Metabolism·Sabine A EmingEdward J Pearce
Aug 14, 2020·Cell Metabolism·Alexander HooftmanLuke A J O'Neill
Oct 8, 2020·Cell Metabolism·Maxim N Artyomov, Jan Van den Bossche
Aug 24, 2021·Gastroenterology·Valerio AzzimatoMyriam Aouadi
Oct 28, 2021·American Journal of Physiology. Cell Physiology·Mohamed Zakaria NassefKarsten Hiller
Oct 27, 2021·Experimental Neurology·Thomas M VigilRichard M Mortensen
Oct 13, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ciana DiskinLuke A J O'Neill

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
Assay
ELISA
PCR
RNA-seq

Software Mentioned

MS Excel
Phantasus
GraphPad Prism
GSEA
ImageJ
Xcalibur
STAR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.