S100A8/A9 mRNA Induction in an Ex Vivo Model of Endotoxin Tolerance: Roles of IL-10 and IFNγ

Fontaine, Mathieu; Planel, Séverine; Peronnet, Estelle; Turrel-Davin, Fanny; Piriou, Vincent; Pachot, Alexandre; Monneret, Guillaume; Lepape, Alain; Venet, Fabienne

doi:10.1371/journal.pone.0100909

Cited by 29 publications

(20 citation statements)

References 52 publications

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“…Endotoxin tolerance (ET) is a critical immune dysfunction related to SS (33). Elevated S100A8 and S100A9 expression has been shown to be induced in ex vivo models of ET, suggesting that these two genes may serve as promising biomarkers of ET and therefore providing valuable information for immunotherapy of patients with SS (34). The present study suggested that S100A9 is closely related to the development and diagnosis of PSS.…”

Section: Discussionmentioning

confidence: 60%

A six‑gene support vector machine classifier contributes to the diagnosis of pediatric septic shock

Long

Yang

2020

Mol Med Report

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Septic shock is induced by an uncontrolled inflammatory immune response to pathogens and the survival rate of patients with pediatric septic shock (PSS) is particularly low, with a mortality rate of 25-50%. The present study explored the mechanisms of PSS using four microarray datasets (GSe26378, GSe26440, GSe13904 and GSe4607) that were obtained from the Gene Expression Omnibus database. Based on the MetaDE package, the consistently differentially expressed genes (DEGs) in the four datasets were screened. Using the WGCNA package, the disease-associated modules and genes were identified. Subsequently, the optimal feature genes were further selected using the caret package. Finally, a support vector machine (SVM) classifier based on the optimal feature genes was built using the e1071 package. Initially, there were 2,699 consistent DEGs across the four datasets. From the 10 significantly stable modules across the datasets, four stable modules (including the magenta, purple, turquoise and yellow modules), in which the consistent DEGs were significantly enriched (P<0.05), were further screened. Subsequently, six optimal feature genes (including cysteine rich transmembrane module containing 1, S100 calcium binding protein A9, solute carrier family 2 member 14, stomatin, uridine phosphorylase 1 and utrophin) were selected from the genes in the four stable modules. Additionally, an effective SVM classifier was constructed based on the six optimal genes. The SVM classifier based on the six optimal genes has the potential to be applied for PSS diagnosis. This may improve the accuracy of early PSS diagnosis and suggest possible molecular targets for interventions.

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Section: Discussionmentioning

confidence: 60%

A six‑gene support vector machine classifier contributes to the diagnosis of pediatric septic shock

Long

Yang

2020

Mol Med Report

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“…S100A8 which is part of the alarmins family is produced by mononuclear cells and consists of calcium binding loops. A recent study indicated that activation of mononuclear cells may increase S100A transcripts ex vivo [ 9 ]. Now, we investigated whether transcripts levels of IL-8 and S100A8 in mononuclear cells on the first postoperative day may be associated with immediate allograft dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-8 Transcripts in Mononuclear Cells Determine Impaired Graft Function after Kidney Transplantation

et al. 2015

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ObjectiveInterleukin-8 (IL-8) has been associated with ischemia reperfusion injury after renal allograft transplantation. Impaired allograft function may cause major impact on patient morbidity and health care costs. We investigated whether transcript levels in mononuclear cells including IL-8 on the first postoperative day may be involved in immediate allograft dysfunction as defined by reduced relative change in plasma creatinine at the first postoperative day.MethodsWe performed a single center, prospective-cohort study of 113 patients receiving kidney transplants. Peripheral blood mononuclear cells were harvested within 24 hours after transplantation. Transcripts were measured using quantitative RT-PCR.ResultsTranscript levels of IL-8 and S100A8 were significantly lower in patients with relative change in plasma creatinine less than 10% at the first postoperative day. Receiver-operator characteristic curves showed that IL-8 predicted the relative change in plasma creatinine less than 10% (area under curve (AUC), 0.80; P = 0.0007). Multivariate analyses showed that lower IL-8 transcripts, longer time on dialysis, higher recipient body mass index and deceased donor type were associated with relative change in plasma creatinine at the first postoperative day less than 10%.ConclusionReduced levels of IL-8 transcripts in peripheral mononuclear cells predict immediate graft dysfunction and delayed graft function.

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“…This raised the question of whether IL-10 may actually contribute to the increased production of TNF-α in CD14-blocked M-MΦ. However, we were able to exclude this possibility by treatment with an IL-10-neutralizing Ab [42], which slightly increased, rather than decreased TNF-α production, both in the presence and absence of the CD14-blocking Ab MEM-18 (Fig. 5f).…”

Section: Resultsmentioning

confidence: 99%

CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor-α Production in a Macrophage Subset

et al. 2019

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In response to GM-CSF or M-CSF, macrophages (MΦ) can acquire pro- or anti-inflammatory properties, respectively. Given the importance of CD14 and Toll-like receptor (TLR) 4 in lipopolysaccharide (LPS)-induced signaling, we studied the effect of anti-CD14 antibody mediated CD14 blockade on LPS-induced cytokine production, signal transduction and on the expression levels of CD14 and TLR4 in GM-MΦ and M-MΦ. We found M-MΦ to express higher levels of both surface antigens and to produce more interferon (IFN)-β and interleukin-10, but less tumor necrosis factor (TNF)-α than GM-MΦ. Blockage of CD14 at high LPS concentrations increased the production of proinflammatory cytokines and decreased that of IFN-β in M-MΦ but not in GM-MΦ. We show that phosphorylation states of signaling molecules of the MyD88 (myeloid differentiation primary response 88), TRIF (TIR-domain-containing adapter-inducing IFN-β) and MAPK (mitogen-activated protein kinase) pathways are not altered in any way that would account for the cytokine overshoot reaction. However, CD14 blockage in M-MΦ decreased TLR4 and CD14 expression levels, regardless of the presence of LPS, indicating that the loss of the surface molecules prevented LPS from initiating TRIF signaling. As TNF-α synthesis was even upregulated under these experimental conditions, we suggest that TRIF is normally involved in restricting LPS-induced TNF-α overproduction. Thus, surface CD14 plays a decisive role in the biological response by determining LPS-induced signaling.

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S100A8/A9 mRNA Induction in an Ex Vivo Model of Endotoxin Tolerance: Roles of IL-10 and IFNγ

Cited by 29 publications

References 52 publications

A six‑gene support vector machine classifier contributes to the diagnosis of pediatric septic shock

A six‑gene support vector machine classifier contributes to the diagnosis of pediatric septic shock

Interleukin-8 Transcripts in Mononuclear Cells Determine Impaired Graft Function after Kidney Transplantation

CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor-α Production in a Macrophage Subset

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