The role and function of IκKα/β in monocyte impairment.

Scientific Reports
Norman J GalbraithSusan Galandiuk

Abstract

Following major trauma, sepsis or surgery, some patients exhibit an impaired monocyte inflammatory response that is characterized by a decreased response to a subsequent bacterial challenge. To investigate this poorly understood phenomenon, we adopted an in-vitro model of endotoxin tolerance utilising primary human CD14 + monocytes to focus on the effect of impairment on IκKα/β, a critical part of the NFκB pathway. Impaired monocytes had decreased IκKα mRNA and protein expression and decreased phosphorylation of the IκKα/β complex. The impaired monocyte secretome demonstrated a distinct cytokine/chemokine footprint from the naïve monocyte, and that TNF-α was the most sensitive cytokine or chemokine in this setting of impairment. Inhibition of IκKα/β with a novel selective inhibitor reproduced the impaired monocyte phenotype with decreased production of TNF-α, IL-6, IL-12p70, IL-10, GM-CSF, VEGF, MIP-1β, TNF-β, IFN-α2 and IL-7 in response to an LPS challenge. Surgical patients with infection also exhibited an impaired monocyte phenotype and had decreased SITPEC, TAK1 and MEKK gene expression, which are important for IκKα/β activation. Our results emphasize that impaired monocyte function is, at least in part, related to dysregul...Continue Reading

References

Nov 1, 1991·The Journal of Clinical Investigation·C MunozJ M Cavaillon
Jul 1, 1990·Statistics in Medicine·Y Hochberg, Y Benjamini
Feb 1, 1993·American Journal of Surgery·W G Cheadle
Jul 1, 1996·Annals of Surgery·M HeinzelmannH C Polk
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Apr 30, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·A-K LichtE Faist
Nov 1, 2003·Biochemical and Biophysical Research Communications·Pedro EscollEduardo López-Collazo
Sep 19, 2006·Shock·Rosanna Di PaolaSalvatore Cuzzocrea
Oct 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Krzysztof LaudanskiRonald G Tompkins
Oct 19, 2006·Critical Care : the Official Journal of the Critical Care Forum·Jean-Marc Cavaillon, Minou Adib-Conquy
Oct 19, 2006·Science's STKE : Signal Transduction Knowledge Environment·Hans Häcker, Michael Karin
Nov 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cornelis van 't VeerTom van der Poll
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carlos del FresnoEduardo López-Collazo
Sep 29, 2009·Trends in Immunology·Subhra K Biswas, Eduardo Lopez-Collazo
Oct 30, 2009·Critical Care Medicine·Sascha Flohé, Martin Scholz
Feb 12, 2011·Critical Care : the Official Journal of the Critical Care Forum·Lulong BoXiaoming Deng
Oct 27, 2011·Critical Care : the Official Journal of the Critical Care Forum·Fanny Turrel-DavinGuillaume Monneret
Nov 24, 2011·The Journal of Experimental Medicine·Wenzhong XiaoUNKNOWN Inflammation and Host Response to Injury Large-Scale Collaborative Research Program
Aug 23, 2012·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Adrian T BilleterHiram C Polk
Nov 16, 2013·Critical Care : the Official Journal of the Critical Care Forum·Eduardo López-Collazo, Carlos del Fresno
Dec 18, 2013·Bioinformatics·Andreas KrämerStuart Tugendreich
Jan 1, 2014·EMBO Reports·Michael Hinz, Claus Scheidereit
Dec 9, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine D PalmerStephanie Jost
Mar 10, 2016·Surgical Infections·Norman GalbraithHiram C Polk
May 8, 2016·Journal of the American Society of Nephrology : JASN·Jianmin ChenChristoph Thiemermann
Nov 30, 2016·Critical Care Clinics·Angela SauaiaErnest E Moore
Feb 28, 2017·Critical Care Medicine·Arie J HoogendijkTom van der Poll
Nov 12, 2017·Immunobiology·Norman J GalbraithSusan Galandiuk
Aug 6, 2018·Surgery·Norman J GalbraithStephen L Barnes

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
FACS
ELISA
enzyme-linked immunosorbent cytokine

Software Mentioned

R
PLS
SigmaPlot
DA
Ingenuity Pathway Analysis ( IPA )
ImageLab
PRISM
SyStat
R Foundation for Statistical Computing

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.