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Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients

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Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients. / Kany, Shinwan; Horstmann, Johann-Philipp; Sturm, Ramona; Mörs, Katharina; Relja, Borna.

In: MEDIAT INFLAMM, Vol. 2018, 2018, p. 1752836.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kany, S, Horstmann, J-P, Sturm, R, Mörs, K & Relja, B 2018, 'Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients', MEDIAT INFLAMM, vol. 2018, pp. 1752836. https://doi.org/10.1155/2018/1752836

APA

Kany, S., Horstmann, J-P., Sturm, R., Mörs, K., & Relja, B. (2018). Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients. MEDIAT INFLAMM, 2018, 1752836. https://doi.org/10.1155/2018/1752836

Vancouver

Kany S, Horstmann J-P, Sturm R, Mörs K, Relja B. Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients. MEDIAT INFLAMM. 2018;2018:1752836. https://doi.org/10.1155/2018/1752836

Bibtex

@article{1a7ccd5d69844737b0e0ff599d52fad2,
title = "Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients",
abstract = "Objective: Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.Measurements and Main Results: Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.Conclusions: This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Cells, Cultured, Humans, Inflammasomes/metabolism, Interleukin-1beta/metabolism, Lipopolysaccharide Receptors/metabolism, Lipopolysaccharides/pharmacology, Macrophages/drug effects, Middle Aged, Monocytes/metabolism, NLR Family, Pyrin Domain-Containing 3 Protein/genetics, Young Adult",
author = "Shinwan Kany and Johann-Philipp Horstmann and Ramona Sturm and Katharina M{\"o}rs and Borna Relja",
year = "2018",
doi = "10.1155/2018/1752836",
language = "English",
volume = "2018",
pages = "1752836",
journal = "MEDIAT INFLAMM",
issn = "0962-9351",
publisher = "Hindawi Publishing Corporation",

}

RIS

TY - JOUR

T1 - Reduced NLRP3 Gene Expression Limits the IL-1β Cleavage via Inflammasome in Monocytes from Severely Injured Trauma Patients

AU - Kany, Shinwan

AU - Horstmann, Johann-Philipp

AU - Sturm, Ramona

AU - Mörs, Katharina

AU - Relja, Borna

PY - 2018

Y1 - 2018

N2 - Objective: Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.Measurements and Main Results: Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.Conclusions: This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.

AB - Objective: Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.Measurements and Main Results: Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.Conclusions: This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Cells, Cultured

KW - Humans

KW - Inflammasomes/metabolism

KW - Interleukin-1beta/metabolism

KW - Lipopolysaccharide Receptors/metabolism

KW - Lipopolysaccharides/pharmacology

KW - Macrophages/drug effects

KW - Middle Aged

KW - Monocytes/metabolism

KW - NLR Family, Pyrin Domain-Containing 3 Protein/genetics

KW - Young Adult

U2 - 10.1155/2018/1752836

DO - 10.1155/2018/1752836

M3 - SCORING: Journal article

C2 - 29861655

VL - 2018

SP - 1752836

JO - MEDIAT INFLAMM

JF - MEDIAT INFLAMM

SN - 0962-9351

ER -