Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock

Jolly, Lucie; Carrasco, Kévin; Derive, Marc; Lemarié, Jérémie; Boufenzer, Amir; Gibot, Sébastien

doi:10.1093/cvr/cvy018

Cited by 36 publications

(37 citation statements)

References 32 publications

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“…TREM-1 blockade using the extracellular domain of TREM-1 fusion IgG or synthetic TREM-1 antagonistic peptide LP17 ameliorated the clinical manifestations of collagen-induced arthritis (CIA) [ 37 ]. In addition, pharmacological inhibition of TREM-1 using LR12, a synthetic inhibitory peptide, protected mice during septic shock in vitro and in vivo [ 38 ], and the LR12 peptide is now under clinical trials in septic patients ( www.clinicaltrials.gov , NCT03158948). Consistent with the previous studies, our results demonstrated that blockade of TREM-1 with LP17 significantly reduced the spontaneous secretion of IL-1β, IL-6 and IL-8 in the neutrophils of AOSD patients, indicating the involvement of TREM-1 in the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Serum sTREM-1 in adult-onset Still’s disease: a novel biomarker of disease activity and a potential predictor of the chronic course

et al. 2020

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Objectives Triggering receptor expressed on myeloid cells-1 (TREM-1) is an amplifier of inflammatory signals. Recently, a soluble form of TREM-1 (sTREM-1) was described. This study aimed to investigate the role of serum sTREM-1 in patients with adult-onset Still’s disease (AOSD). Methods Serum sTREM-1 levels were detected in 108 AOSD patients, 88 RA patients and 112 healthy controls (HC). The correlations of sTREM-1 with disease activity, clinical characteristics and laboratory parameters in AOSD patients were analysed by the Spearman correlation test. Risk factors for the chronic course of AOSD were evaluated by multivariate logistic regression analysis. Results AOSD patients had significantly higher serum sTREM-1 levels than RA patients and HC, and serum sTREM-1 levels were correlated with the systemic score, ferritin, leucocyte count, CRP, IL-1β and IL-6. The elevation in the initial sTREM-1 level by itself could discriminate patients developing the chronic course from patients developing the nonchronic course. Moreover, an elevated sTREM-1 level (> 526.4475 pg/ml) was an independent risk factor for the chronic course in active AOSD patients. Furthermore, interfering with TREM-1 engagement led to reductions in the secretion of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, in neutrophils and monocytes from active AOSD patients. Conclusion Serum sTREM-1 levels are correlated with disease activity, and an elevation in the initial serum sTREM-1 level is a potential predictor of the chronic course in AOSD patients, which currently provides the best predictive model for identifying patients prone to developing the chronic course of AOSD.

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Section: Discussionmentioning

confidence: 99%

Serum sTREM-1 in adult-onset Still’s disease: a novel biomarker of disease activity and a potential predictor of the chronic course

et al. 2020

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“…Leukocyte trafficking was analyzed by flow cytometry as previously described [33]. The spleen and liver were crushed in HBSS and filtered on a 70-μm nylon filter.…”

Section: Methodsmentioning

confidence: 99%

Bone marrow vs Wharton’s jelly mesenchymal stem cells in experimental sepsis: a comparative study

Laroye

Boufenzer²,

Jolly

et al. 2019

Stem Cell Res Ther

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Background The use of mesenchymal stem cells (MSCs) is being extensively studied in clinical trials in the setting of various diseases including diabetes, stroke, and progressive multiple sclerosis. The unique immunomodulatory properties of MSCs also point them as a possible therapeutic tool during sepsis and septic shock, a devastating syndrome associated with 30–35% mortality. However, MSCs are not equal regarding their activity, depending on their tissue origin. Here, we aimed at comparing the in vivo properties of MSCs according to their tissue source (bone marrow (BM) versus Wharton’s jelly (WJ)) in a murine cecal ligation and puncture (CLP) model of sepsis that mimics a human peritonitis. We hypothesized that MSC properties may vary depending on their tissue source in the setting of sepsis. Methods CLP, adult, male, C57BL/6 mice were randomized in 3 groups receiving respectively 0.25 × 10 6 BM-MSCs, 0.25 × 10 6 WJ-MSCs, or 150 μL phosphate-buffered saline (PBS) intravenously 24 h after the CLP procedure. Results We observed that both types of MSCs regulated leukocyte trafficking and reduced organ dysfunction, while only WJ-MSCs were able to improve bacterial clearance and survival. Conclusion This study highlights the importance to determine the most appropriate source of MSCs for a given therapeutic indication and suggests a better profile for WJ-MSCs during sepsis.

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“…Myeloid cell trigger receptor-1 (TREM-1) is a member of the immunoglobulin super receptor family mainly expressed on the surface of myeloid cells such as neutrophils and monocytes/macrophages [16]. Soluble TREM-1 (sTREM-1), one of the two forms of TREM-1, has been reported as a novel and strong indicator of pneumonia [17].…”

Section: Introductionmentioning

confidence: 99%

Significance of sTREM-1 in early prediction of ventilator-associated pneumonia in neonates: a single-center, prospective, observational study

Zhao

Yang

et al. 2020

BMC Infect Dis

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Background: To evaluate whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) can be used as an early predictor of ventilator-associated pneumonia (VAP). Methods: Ventilated neonatal patients admitted into the neonatology department between January 2017 and January 2018 were divided into VAP (n = 30) and non-VAP (n = 30) groups. Serum sTREM, procalcitonin (PCT), Creactive protein and interleukin-6 levels were measured at 0, 24, 72, and 120 h after initiation of mechanical ventilation (MV). Correlations between blood biomarker concentrations and VAP occurrence were analyzed. Predictive factors for VAP were identified by logistic regression analysis and Hosmer-Lemeshow test, and the predictive value of sTREM-1 and biomarker combinations for VAP was determined by receiver operating characteristic curve analysis. Results: The serum sTREM-1 concentration was significantly higher in the VAP group than in the non-VAP group after 72 and 120 h of MV (72 h: 289.5 (179.6-427.0) vs 202.9 (154.8-279.6) pg/ml, P < 0.001; 120 h: 183.9 (119.8-232.1) vs 141.3 (99.8-179.1) pg/ml, P = 0.042). The area under the curve (AUC) for sTREM-1 at 72 h was 0.902 with a sensitivity of 90% and specificity of 77% for the optimal cutoff value of 165.05 pg/ml. Addition of PCT to sTERM-1 at 72 h further improved the predictive value, with this combination having an AUC of 0.971 (95% confidence interval: 0.938-1.000), sensitivity of 0.96, specificity of 0.88, and Youden index of 0.84. Conclusion: sTREM-1 is a reliable predictor of VAP in neonates, and combined measurement of serum levels of sTREM-1 and PCT after 72 h of MV provided the most accurate prediction of VAP in neonatal patients.

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Targeted endothelial gene deletion of triggering receptor expressed on myeloid cells-1 protects mice during septic shock

Cited by 36 publications

References 32 publications

Serum sTREM-1 in adult-onset Still’s disease: a novel biomarker of disease activity and a potential predictor of the chronic course

Serum sTREM-1 in adult-onset Still’s disease: a novel biomarker of disease activity and a potential predictor of the chronic course

Bone marrow vs Wharton’s jelly mesenchymal stem cells in experimental sepsis: a comparative study

Significance of sTREM-1 in early prediction of ventilator-associated pneumonia in neonates: a single-center, prospective, observational study

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