The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans

Rahajeng N Tunjungputri; Yang Li; Philip G de Groot; Charles A Dinarello; Sanne P Smeekens; Martin Jaeger; Marije Doppenberg-Oosting; Milou Cruijsen; Heidi Lemmers; Helga Toenhake-Dijkstra; Raul Aguirre-Gamboa; Vinod Kumar; Cisca Wijmenga; Leo A B Joosten; Mihai G Netea; Andre van der Ven; Quirijn de Mast

doi:10.1055/s-0038-1675603

The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans

Rahajeng N Tunjungputri
, Yang Li
, Philip G de Groot
, Charles A Dinarello
, Sanne P Smeekens
, Martin Jaeger
, Marije Doppenberg-Oosting
, Milou Cruijsen
, Heidi Lemmers
, Helga Toenhake-Dijkstra
, Raul Aguirre-Gamboa
, Vinod Kumar
, Cisca Wijmenga
, Leo A B Joosten
, Mihai G Netea
, Andre van der Ven
, Quirijn de Mast^*

^*Corresponding author for this work

Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Research output: Contribution to journal › Article › Academic › peer-review

38 Citations (Scopus)

Abstract

Background Inflammation and coagulation are key processes in cardiovascular diseases (CVDs). The Canakinumab Anti-inflammatory Thrombosis Outcome Study trial affirmed the importance of inflammation in CVD by showing that inhibition of the interleukin (IL)-1 beta pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1 beta-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation-and especially IL-1 beta-in a cohort of healthy volunteers.

Methods We used data from the 500-Human Functional Genomics cohort, which consists of approximately 500 Caucasian, healthy individuals. We determined associations of plasma levels of IL-1 beta and other inflammatory proteins with platelet number and reactivity, the association of platelet reactivity with ex vivo cytokine production as well as the impact of genetic variations through a genome-wide association study (GWAS).

Results Platelets were associated with IL-1 beta on different levels. First, platelet number was positively associated with plasma IL-1 beta concentrations (p = 8.9 x 10(-9)) and inversely with concentrations of alpha-1-anti-trypsin (p = 1.04 x 10(-18)), which is a known antagonist of IL-1 beta. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1 beta and IL-6 production. Third, several platelet single-nucleotide polymorphisms (SNPs) were associated with cytokine production and there was a significant platelet SNP enrichment in specific biological important pathways. Finally, platelet SNPs were enriched among SNPs earlier identified in GWAS studies in blood-related diseases and immune-mediated diseases.

Conclusion This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1 beta-mediated inflammation.

Original language	English
Pages (from-to)	2112-2125
Number of pages	14
Journal	Thrombosis and Haemostasis
Volume	118
Issue number	12
DOIs	https://doi.org/10.1055/s-0038-1675603
Publication status	Published - Dec-2018

Keywords

platelet immunology
inflammation
infectious diseases
cytokines
platelet physiology
FUNCTIONAL GENOMICS APPROACH
ACTIVATED PLATELETS
CYTOKINE PRODUCTION
CIGARETTE-SMOKING
DISEASE
PROTEIN
LOCI
ALPHA-1-ANTITRYPSIN
AGGREGATION
INHIBITION

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The Inter-Relationship of Platelets with Interleukin-1
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Tunjungputri, R. N., Li, Y., de Groot, P. G., Dinarello, C. A., Smeekens, S. P., Jaeger, M., Doppenberg-Oosting, M., Cruijsen, M., Lemmers, H., Toenhake-Dijkstra, H., Aguirre-Gamboa, R., Kumar, V., Wijmenga, C., Joosten, L. A. B., Netea, M. G., van der Ven, A., & de Mast, Q. (2018). The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans. Thrombosis and Haemostasis, 118(12), 2112-2125. https://doi.org/10.1055/s-0038-1675603

@article{1d758b58dd8d4ac2933f48737c527d13,

title = "The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans",

abstract = "Background Inflammation and coagulation are key processes in cardiovascular diseases (CVDs). The Canakinumab Anti-inflammatory Thrombosis Outcome Study trial affirmed the importance of inflammation in CVD by showing that inhibition of the interleukin (IL)-1 beta pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1 beta-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation-and especially IL-1 beta-in a cohort of healthy volunteers.Methods We used data from the 500-Human Functional Genomics cohort, which consists of approximately 500 Caucasian, healthy individuals. We determined associations of plasma levels of IL-1 beta and other inflammatory proteins with platelet number and reactivity, the association of platelet reactivity with ex vivo cytokine production as well as the impact of genetic variations through a genome-wide association study (GWAS).Results Platelets were associated with IL-1 beta on different levels. First, platelet number was positively associated with plasma IL-1 beta concentrations (p = 8.9 x 10(-9)) and inversely with concentrations of alpha-1-anti-trypsin (p = 1.04 x 10(-18)), which is a known antagonist of IL-1 beta. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1 beta and IL-6 production. Third, several platelet single-nucleotide polymorphisms (SNPs) were associated with cytokine production and there was a significant platelet SNP enrichment in specific biological important pathways. Finally, platelet SNPs were enriched among SNPs earlier identified in GWAS studies in blood-related diseases and immune-mediated diseases.Conclusion This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1 beta-mediated inflammation.",

keywords = "platelet immunology, inflammation, infectious diseases, cytokines, platelet physiology, FUNCTIONAL GENOMICS APPROACH, ACTIVATED PLATELETS, CYTOKINE PRODUCTION, CIGARETTE-SMOKING, DISEASE, PROTEIN, LOCI, ALPHA-1-ANTITRYPSIN, AGGREGATION, INHIBITION",

author = "Tunjungputri, \{Rahajeng N\} and Yang Li and \{de Groot\}, \{Philip G\} and Dinarello, \{Charles A\} and Smeekens, \{Sanne P\} and Martin Jaeger and Marije Doppenberg-Oosting and Milou Cruijsen and Heidi Lemmers and Helga Toenhake-Dijkstra and Raul Aguirre-Gamboa and Vinod Kumar and Cisca Wijmenga and Joosten, \{Leo A B\} and Netea, \{Mihai G\} and \{van der Ven\}, Andre and \{de Mast\}, Quirijn",

note = "Georg Thieme Verlag KG Stuttgart · New York.",

year = "2018",

month = dec,

doi = "10.1055/s-0038-1675603",

language = "English",

volume = "118",

pages = "2112--2125",

journal = "Thrombosis and Haemostasis",

issn = "0340-6245",

publisher = "GEORG THIEME VERLAG KG",

number = "12",

}

Tunjungputri, RN, Li, Y, de Groot, PG, Dinarello, CA, Smeekens, SP, Jaeger, M, Doppenberg-Oosting, M, Cruijsen, M, Lemmers, H, Toenhake-Dijkstra, H, Aguirre-Gamboa, R, Kumar, V , Wijmenga, C, Joosten, LAB, Netea, MG, van der Ven, A & de Mast, Q 2018, 'The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans', Thrombosis and Haemostasis, vol. 118, no. 12, pp. 2112-2125. https://doi.org/10.1055/s-0038-1675603

TY - JOUR

T1 - The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans

AU - Tunjungputri, Rahajeng N

AU - Li, Yang

AU - de Groot, Philip G

AU - Dinarello, Charles A

AU - Smeekens, Sanne P

AU - Jaeger, Martin

AU - Doppenberg-Oosting, Marije

AU - Cruijsen, Milou

AU - Lemmers, Heidi

AU - Toenhake-Dijkstra, Helga

AU - Aguirre-Gamboa, Raul

AU - Kumar, Vinod

AU - Wijmenga, Cisca

AU - Joosten, Leo A B

AU - Netea, Mihai G

AU - van der Ven, Andre

AU - de Mast, Quirijn

N1 - Georg Thieme Verlag KG Stuttgart · New York.

PY - 2018/12

Y1 - 2018/12

N2 - Background Inflammation and coagulation are key processes in cardiovascular diseases (CVDs). The Canakinumab Anti-inflammatory Thrombosis Outcome Study trial affirmed the importance of inflammation in CVD by showing that inhibition of the interleukin (IL)-1 beta pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1 beta-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation-and especially IL-1 beta-in a cohort of healthy volunteers.Methods We used data from the 500-Human Functional Genomics cohort, which consists of approximately 500 Caucasian, healthy individuals. We determined associations of plasma levels of IL-1 beta and other inflammatory proteins with platelet number and reactivity, the association of platelet reactivity with ex vivo cytokine production as well as the impact of genetic variations through a genome-wide association study (GWAS).Results Platelets were associated with IL-1 beta on different levels. First, platelet number was positively associated with plasma IL-1 beta concentrations (p = 8.9 x 10(-9)) and inversely with concentrations of alpha-1-anti-trypsin (p = 1.04 x 10(-18)), which is a known antagonist of IL-1 beta. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1 beta and IL-6 production. Third, several platelet single-nucleotide polymorphisms (SNPs) were associated with cytokine production and there was a significant platelet SNP enrichment in specific biological important pathways. Finally, platelet SNPs were enriched among SNPs earlier identified in GWAS studies in blood-related diseases and immune-mediated diseases.Conclusion This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1 beta-mediated inflammation.

AB - Background Inflammation and coagulation are key processes in cardiovascular diseases (CVDs). The Canakinumab Anti-inflammatory Thrombosis Outcome Study trial affirmed the importance of inflammation in CVD by showing that inhibition of the interleukin (IL)-1 beta pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1 beta-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation-and especially IL-1 beta-in a cohort of healthy volunteers.Methods We used data from the 500-Human Functional Genomics cohort, which consists of approximately 500 Caucasian, healthy individuals. We determined associations of plasma levels of IL-1 beta and other inflammatory proteins with platelet number and reactivity, the association of platelet reactivity with ex vivo cytokine production as well as the impact of genetic variations through a genome-wide association study (GWAS).Results Platelets were associated with IL-1 beta on different levels. First, platelet number was positively associated with plasma IL-1 beta concentrations (p = 8.9 x 10(-9)) and inversely with concentrations of alpha-1-anti-trypsin (p = 1.04 x 10(-18)), which is a known antagonist of IL-1 beta. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1 beta and IL-6 production. Third, several platelet single-nucleotide polymorphisms (SNPs) were associated with cytokine production and there was a significant platelet SNP enrichment in specific biological important pathways. Finally, platelet SNPs were enriched among SNPs earlier identified in GWAS studies in blood-related diseases and immune-mediated diseases.Conclusion This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1 beta-mediated inflammation.

KW - platelet immunology

KW - inflammation

KW - infectious diseases

KW - cytokines

KW - platelet physiology

KW - FUNCTIONAL GENOMICS APPROACH

KW - ACTIVATED PLATELETS

KW - CYTOKINE PRODUCTION

KW - CIGARETTE-SMOKING

KW - DISEASE

KW - PROTEIN

KW - LOCI

KW - ALPHA-1-ANTITRYPSIN

KW - AGGREGATION

KW - INHIBITION

U2 - 10.1055/s-0038-1675603

DO - 10.1055/s-0038-1675603

M3 - Article

C2 - 30453346

SN - 0340-6245

VL - 118

SP - 2112

EP - 2125

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

IS - 12

ER -

The Inter-Relationship of Platelets with Interleukin-1 beta-Mediated Inflammation in Humans

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