Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

Peng, Liang-shan; Li, Juan; Zhou, Gaosheng; Deng, Liehua; Yao, Heng‐Chen

doi:10.5847/wjem.j.1920-8642.2015.02.007

Cited by 16 publications

(17 citation statements)

References 30 publications

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“…The soluble form of the triggering receptor expressed on myeloid cells (TREM)-1 is a member of the immunoglobulin family of receptors that are expressed on myeloid cells and act synergistically with TLR. TREM-1 is a BM with diagnostic performance and prognostic value [ 53 , 54 , 55 , 56 , 57 ]. The association between its genomic variability and sepsis is less defined.…”

Section: Cellular Receptorsmentioning

confidence: 99%

The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

Georgescu

Grigorescu

Chirteș

et al. 2017

The Journal of Critical Care Medicine

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Sepsis is an injurious systemic host response to infection, which can often lead to septic shock and death. Recently, the immune-pathogenesis and genomics of sepsis have become a research topic focusing on the establishment of diagnostic and prognostic biomarkers. As yet, none have been identified as having the necessary specificity to be used independently of other factors in this respect. However the accumulation of current evidence regarding genetic variations, especially the single nucleotide polymorphisms (SNPs) of cytokines and other innate immunity determinants, partially explains the susceptibility and individual differences of patients with regard to the evolution of sepsis. This article outlines the role of genetic variation of some serum proteins which have the potential to be used as biomarker values in evaluating sepsis susceptibility and the progression of the condition.

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Section: Cellular Receptorsmentioning

confidence: 99%

The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

Georgescu

Grigorescu

Chirteș

et al. 2017

The Journal of Critical Care Medicine

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“…A TREM-1 genetic polymorphism rs2234246 has recently been described that correlates with susceptibility to septic shock in the Chinese Han population, 50 though the implications of this for membrane bound and soluble TREM-1 are currently unclear. Soluble TREM-1 has also been utilized as a biomarker for disease severity, particularly in pneumonia and septic shock.…”

Section: Articlesmentioning

confidence: 99%

Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors

et al. 2017

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on neutrophils and monocyte/macrophages and amplifies Toll-like receptor-mediated inflammation during infection. TREM-1 also exists in an antagonistic soluble form (sTREM-1) that has been used as a peripheral biomarker in sepsis, though the mechanisms of its release are not entirely clear. The requirement of TREM-1 in single microbial infections is controversial, with some studies showing a protective role and others a contribution to immunopathology. Furthermore, the role of membrane-bound and sTREM-1 in polygenic infections is currently unknown. In a mouse co-infection model where preceding viral infection greatly enhances bacteria co-infection, we now determine a mechanisms for the striking increase in sTREM-1 and the loss of TREM-1 on surface of neutrophils. We identified a matrix metalloproteinase (MMP)-9 cleavage site in TREM-1 and that the increase of MMP-9 in bronchoalveolar lavage fluid mirrors sTREM-1 release. In vitro studies with neutrophils and MMP-9 and the reduction of sTREM-1 in vivo after MMP-9 inhibition verifies that this enzyme cleaves TREM-1. Intriguingly, MMP-9 inhibition significantly reduces bacterial load and ensuing immunopathology in a co-infection model. This highlights MMP-9 inhibition as a potential therapeutic via blocking cleavage of TREM-1.

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“…Given the high frequency of the polymorphism in the general population (about 50%), this result could be of high interest in further personalized medicine strategies for stratifying patients according to their risk to the above pathologies. In this context, it is important to note that a previous study has associated the minor allele of the SNP rs2234246 with an increased 3.1 odds ratio for septic shock [ 39 ]. This finding strengthens our hypothesis on the utility of the polymorphisms located in TREM-1 gene in risk stratification.…”

Section: Discussionmentioning

confidence: 99%

TREM-1 SNP rs2234246 regulates TREM-1 protein and mRNA levels and is associated with plasma levels of L-selectin

et al. 2017

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High levels of TREM-1 are associated with cardiovascular and inflammatory diseases risks and the most recent studies have showed that TREM-1 deletion or blockade is associated with up to 60% reduction of the development of atherosclerosis. So far, it is unknown whether the levels of TREM-1 protein are genetically regulated. Moreover, TREM family receptors have been suggested to regulate the cellular adhesion process. The goal of this study was to investigate whether polymorphisms within TREM-1 are regulating the variants of serum TREM-1 levels and the expression levels of their mRNA. Furthermore, we aimed to point out associations between polymorphisms on TREM-1 and blood levels of selectins. Among the 10 SNPs studied, the minor allele T of rs2234246, was associated with increased sTREM-1 in the discovery population (p-value = 0.003), explaining 33% of its variance, and with increased levels of mRNA (p-value = 0.007). The same allele was associated with increased soluble L-selectin levels (p-value = 0.011). The higher levels of sTREM-1 and L-selectin were confirmed in the replication population (p-value = 0.0007 and p-value = 0.018 respectively). We demonstrated for the first time one SNP on TREM-1, affecting its expression levels. These novel results, support the hypothesis that TREM-1 affects monocytes extravasation and accumulation processes leading to atherogenesis and atherosclerotic plaque progression, possibly through increased inflammation and subsequent higher expression of sL-selectin.

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Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

Cited by 16 publications

References 30 publications

The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors

TREM-1 SNP rs2234246 regulates TREM-1 protein and mRNA levels and is associated with plasma levels of L-selectin

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