miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function

Abstract

Background. Recent literature has reported the use of circulating microRNAs (miRNAs) as biomarkers for sepsis. Immune cells play an essential role in the pathophysiology of sepsis. The aim of this prospective study was to identify miRNAs in peripheral blood mononuclear cells (PBMC) that could differentiate between sepsis and infection based on Sepsis-3 definition. Methods. A total of 62 patients (41 with sepsis and 21 with infection suffering from pneumonia but without sepsis) and 20 healthy controls were enrolled into the study. PBMC at admission were examined for a panel of 4 miRNAs (miR-10a, miR-17, miR-27a, and miR-125b), which have been documented to participate in inflammatory response in immune cells, via qRT-PCR. Data were validated in a mouse model of sepsis induced via cecal ligation and puncture (CLP) and THP-1 monocytes. Results. miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with patients with infection and healthy controls. miR-10a levels were negatively correlated with disease severity scores as well as levels for c-reactive protein and procalcitonin. In addition, low miR-10a expression had a diagnostic value for sepsis and a prognostic value for 28-day mortality in receiving operating characteristic analysis. Compared with infection patients and healthy controls, PBMC from sepsis patients also had higher levels of mitogen-activated kinase kinase kinase 7 (MAP3K7), a known target protein of miR-10a and an activator of the NF-κB pathway. In the mouse model of CLP-induced sepsis, miR-10a levels in PBMC were significantly decreased as early as 8 h after CLP. Overexpression of miR-10a in THP-1 cells significantly reduced the expression of MAP3K7 and proinflammatory cytokines including IL-6, TNF-α, and MCP-1. Conclusions. PBMC miR-10a levels are decreased in sepsis and negatively correlated with the disease severity. Levels of miR-10a could distinguish between sepsis and infection and predict 28-day mortality. miR-10a plays an anti-inflammatory role in the pathogenesis of sepsis.

Low-Density Granulocyte Contamination From Peripheral Blood Mononuclear Cells of Patients With Sepsis and How to Remove It – A Technical Report

“…This is an explanation for our observation, that the number of low-density granulocytes co-purifying with the PBMC fraction varies highly between patients. Although some of the studies depicting the problem of contaminating, co-purifying low-density granulocytes have been published a decade ago, it is still common practice today to use density gradient centrifugation for PBMC isolation from patients with sepsis (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). This goes along with a lack of reported information on the isolation purity and identification of the contained cell types.…”

DNA Methylation Analysis to Unravel Altered Genetic Pathways Underlying Early Onset and Late Onset Neonatal Sepsis. A Pilot Study

“…It would be interesting to measure DUSP22 methylation in a cohort of neonatal septic patients in order to evaluate its potential as prognostic biomarkers in neonatal sepsis. Regarding MIR10A , it has been shown that miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with non-septic patients with infection, and with healthy controls ( 58 ). Moreover, miR-10a levels were found to predict 28-day mortality and negatively correlate with disease severity as well as levels for C-reactive protein, procalcitonin, and inflammatory cytokines such as IL-6, TNF-α, and MCP-1 ( 58 ).…”

“…Regarding MIR10A , it has been shown that miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with non-septic patients with infection, and with healthy controls ( 58 ). Moreover, miR-10a levels were found to predict 28-day mortality and negatively correlate with disease severity as well as levels for C-reactive protein, procalcitonin, and inflammatory cytokines such as IL-6, TNF-α, and MCP-1 ( 58 ). Regarding MIR886 , it has been shown that miR-886-5p is increased in human monocyte-derived macrophages as a response to mycobacterial infection at 48 h ( 59 ), and the isoform hsa-miR-886-3p was present at higher levels in PBMCs from critically ill patients infected with H1N1 influenza virus than PBMCs from healthy controls ( 60 ).…”

Extracellular Vesicles Derived From Regeneration Associated Cells Preserve Heart Function After Ischemia-Induced Injury

“…The immunomodulatory and immunosuppressive function of RACev may thus be associated with Treg-derived EV secretion, as Tregs modify the host antigen-presenting cell function via miR-142-3p (2285-fold upregulated in RACev), and EVs may escape T cell recognition as shown previously ( Supplementary Figure 3E ) ( 39 ). The miRs have broad functions in immune regulation, for example, miR-10a, miR-21, miR-24 are expressed in immune cells and function as “fine-tuners” for innate and adaptive immune responses ( 40 , 41 ). In adaptive immunity, they are implicated in the biological processes including pathways involved in the T and B cells central and peripheral tolerance, as well as their function ( 40 ).…”