Inflammation and ER stress downregulate BDH2 expression and dysregulate intracellular iron in macrophages

Journal of Immunology Research
Susu M ZughaierNael A McCarty

Abstract

Macrophages play a very important role in host defense and in iron homeostasis by engulfing senescent red blood cells and recycling iron. Hepcidin is the master iron regulating hormone that limits dietary iron absorption from the gut and limits iron egress from macrophages. Upon infection macrophages retain iron to limit its bioavailability which limits bacterial growth. Recently, a short chain butyrate dehydrogenase type 2 (BDH2) protein was reported to contain an iron responsive element and to mediate cellular iron trafficking by catalyzing the synthesis of the mammalian siderophore that binds labile iron; therefore, BDH2 plays a crucial role in intracellular iron homeostasis. However, BDH2 expression and regulation in macrophages have not yet been described. Here we show that LPS-induced inflammation combined with ER stress led to massive BDH2 downregulation, increased the expression of ER stress markers, upregulated hepcidin expression, downregulated ferroportin expression, caused iron retention in macrophages, and dysregulated cytokine release from macrophages. We also show that ER stress combined with inflammation synergistically upregulated the expression of the iron carrier protein NGAL and the stress-inducible heme deg...Continue Reading

References

Nov 20, 1986·Journal of Immunological Methods·D Gerlier, N Thomasset
Aug 29, 2002·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Roberto Pecoits-FilhoPeter Stenvinkel
Oct 11, 2002·Free Radical Biology & Medicine·Or Kakhlon, Z Ioav Cabantchik
Feb 18, 2006·Nature Chemical Biology·Michael A FischbachChristopher T Walsh
Aug 28, 2007·International Journal of Nanomedicine·Viroj Wiwanitkit
Feb 23, 2008·Molecular Endocrinology·Jinhui ZhangXiaoli Chen
Jun 4, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Milan TheurlGuenter Weiss
Aug 6, 2008·Journal of the American Chemical Society·Rebecca J AbergelKenneth N Raymond
Oct 2, 2008·European Journal of Clinical Investigation·T M El-AchkarP C Dagher
Aug 15, 2009·Science·Chiara VecchiAntonello Pietrangelo
Nov 12, 2009·Cell Stress & Chaperones·Parisa BahmaniMehryar Habibi Roudkenar
Nov 19, 2009·Journal of Biochemistry·Yoichiro NakayamaTomomi Gotoh
Dec 30, 2009·European Journal of Immunology·Stefania RecalcatiGaetano Cairo
Mar 20, 2010·World Journal of Gastroenterology : WJG·Palash MandalLaura E Nagy
Jun 1, 2010·Haematologica·Gianfranca CornaPatrizia Rovere-Querini
Jun 29, 2010·Nature Chemical Biology·Guanhu BaoJonathan Barasch
Aug 14, 2010·Current Drug Targets·Stephan ImmenschuhSebastian Mueller
Sep 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Palash MandalLaura E Nagy
Oct 5, 2010·Annual Review of Medicine·Tomas Ganz, Elizabeta Nemeth
Jan 5, 2011·Biochemistry Research International·Susana J OliveiraJorge P Pinto
Feb 4, 2011·Current Opinion in Cell Biology·Soledad MatusClaudio Hetz
Feb 15, 2011·The Journal of Clinical Investigation·Anca SindrilaruKarin Scharffetter-Kochanek
Feb 26, 2011·The Biochemical Journal·Jian Wang, Kostas Pantopoulos
Apr 26, 2011·Trends in Immunology·Gaetano CairoMassimo Locati
Jul 15, 2011·International Journal of Inflammation·Tomomi GotohYuichi Oike
Apr 20, 2012·Biochimica Et Biophysica Acta·Subhankar ChakrabortySurinder K Batra
Apr 25, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Zhuoming LiuL Devireddy

❮ Previous
Next ❯

Citations

Dec 25, 2016·Biological Trace Element Research·Giovanni CorsettiFrancesco S Dioguardi
May 17, 2017·Frontiers in Immunology·Alexandra WillemetzFrançois Canonne-Hergaux
Aug 16, 2019·The Journal of Biological Chemistry·Inna A NikonorovaTracy G Anthony
Jul 2, 2020·Journal of Experimental & Clinical Cancer Research : CR·Jia-Zhou LiuWan-Jiang Xue
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Yuting FuSiqin Bao
Jan 3, 2021·Seminars in Cell & Developmental Biology·David HaschkaGünter Weiss

❮ Previous
Next ❯

Methods Mentioned

BETA
protein assay
glycosylation

Software Mentioned

Prism
Excel

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.