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Inflammation-related gene expression profiles of salivary extracellular vesicles in patients with head trauma.

ABSTRACT: At present, there is no reliable biomarker for the diagnosis of traumatic brain injury (TBI). Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential biomarkers for diagnosis of TBI and evaluation of TBI severity. We hypothesize that the genetic profile of salivary extracellular vesicles in patients with head trauma differs from that in uninjured subjects. Findings from this hypothesis would help investigate the severity of TBI. This study included 19 subjects, consisting of seven healthy controls who denied history of head trauma, six patients diagnosed with concussion injury from an outpatient concussion clinic, and six patients with TBI who received treatment in the emergency department within 24 hours after injury. Real-time PCR analysis of salivary extracellular vesicles in participants was performed using TaqMan Human Inflammation array. Gene expression analysis revealed nine upregulated genes in emergency department patients (LOX5, ANXA3, CASP1, IL2RG, ITGAM, ITGB2, LTA4H, MAPK14, and TNFRSF1A) and 13 upregulated genes in concussion clinic patients compared with healthy participants (ADRB1, ADRB2, BDKRB1, HRH1, HRH2, LTB4R2, LTB4R, PTAFR, CYSLTR1, CES1, KLK1, MC2R, and PTGER3). Each patient group had a unique profile. Comparison between groups showed that 15 inflammation-related genes had significant expression change. Our results indicate that inflammation biomarkers can be used for diagnosis of TBI and evaluation of disease severity. This study was approved by the Institutional Review Board on December 18, 2015 (approval No. 0078-12) and on June 9, 2016 (approval No. 4093-16).

SUBMITTER: Cheng Y

PROVIDER: S-EPMC6975135 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Inflammation-related gene expression profiles of salivary extracellular vesicles in patients with head trauma.

Cheng Yan Y Pereira Mandy M Raukar Neha P NP Reagan John L JL Quesenberry Mathew M Goldberg Laura L Borgovan Theodor T LaFrance Jr W Curt WC Dooner Mark M Deregibus Maria M Camussi Giovanni G Ramratnam Bharat B Quesenberry Peter P

Neural regeneration research 20200401 4

At present, there is no reliable biomarker for the diagnosis of traumatic brain injury (TBI). Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential biomarkers for diagnosis of TBI and evaluation of TBI severity. We hypothesize that the genetic profile of salivary extracellular vesicles in patients with head trauma differs from that in uninjured subjects. Findings from this hypothesis would help investigate the severity of TBI. Th ...[more]

PMID: 31638091

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Project description:Background and aimsSaliva is essential for the proper dilution and distribution of taste molecules on the tongue. It harbors extracellular vesicles (EVs), which mediate cell-cell communication. Changes in the composition of salivary EVs may arise under obese conditions and may potentially be involved in taste sensation and dysregulated eating behavior. Therefore, this study addresses the relationship between the size and concentration of salivary EVs and metabolic shifts in obesity or factors of taste sensation.Materials and methodsA total of 119 participants in the Obese Taste Bud (OTB) Study were included, who performed a standardized taste test, underwent taste bud density assessment, and were phenotypically characterized for anthropometrics, blood- and saliva adipokine levels, and various metabolic factors. Utilizing size exclusion chromatography followed by ultrafiltration, EVs were extracted from 2 mL of actively secreted saliva. EVs were characterized using nanoparticle tracking analyses, Western blot, and scanning transmission electron microscopy. Finally, group comparisons and bivariate correlation analyses were conducted.ResultsAmong the total cohort, the median size of salivary EVs was 190.05 nm, and the overall concentration ranged from 1.4 × 107 to 1.76 × 109 per mL of saliva. The size range and concentration of EVs per mL are negatively correlated (p = 0.0002, r = -0.264). Comparing lean participants (mean rank of 45.98) with those presenting obesity (mean rank of 34.46), a significant difference in the salivary EV content was observed (p = 0.029). Body weight, BMI, arm and calf circumferences, as well as the percentage of body fat were all negatively related to the concentration of EVs in all study participants (all p < 0.05, r > -0.2). No associations were found between the EV parameters and taste perception but serum alkaline phosphatase levels were negatively correlated (p = 0.007, r = -0.284) and adiponectin serum levels were positively correlated to the EV concentration (p = 0.036, r = 0.208).ConclusionThe current study provides evidence for the relation between salivary EVs and anthropometric as well as metabolic parameters of obesity. This can provide the basis for further research on the cargo of salivary EVs and how they may influence taste sensation, and may elucidate their potential connection to altered eating habits in obesity.

Project description:Aimaliva extracellular vesicles (EVs) serve as a significant reservoir of biomarkers that may be of clinical use in disease diagnosis. Saliva, however, contains EVs of both host- and bacterial- origin. Identifying suitable EVs for disease diagnosis involves enriching host EVs and limiting non-host contamination with effective isolation methods. The objectives of this research were: (1) to evaluate the salivary EVs enrichment in 12 periodontally healthy patients by two different methods: size exclusion chromatography (SEC) and bead-based immunoaffinity capture (EXO-NET®); (2) to analyze the variance expression of inflammatory cytokines in EXO-NET-enriched EVs, comparing individuals with periodontitis (n = 20) to non-periodontitis (n = 12).MethodsWhole unstimulated saliva samples were collected from 12 periodontally healthy and 20 periodontitis patients. EVs were isolated from the 12 non-periodontitis patients using SEC (referred to as SEC-EVs) and EXO-NET (referred to as EXO-NET EVs), after which their total protein content, 37 EV surface markers, and bacterial pathogens expression were compared. Subsequently, the inflammatory cytokines expression levels (interleukin-IL-6, IL-1β, IL-8, and IL-10) in EXO-NET EVs were measured for non-periodontitis and periodontitis.ResultsEXO-NET EVs contained more EV-specific protein and substantially higher expression of EV surface markers (CD9, CD81, CD63), but less pathogenic DNA was detected compared to that in SEC-EVs. Additionally, EXO-NET EVs from periodontitis patients contained higher amounts of IL-6 and IL-8, and decreased IL-10, compared to those from non-periodontitis patients.ConclusionThe findings suggest that immunoaffinity capture (EXO-NET) is a dependable method for salivary EVs enrichment, resulting in a higher yield of host EVs with reduced bacterial DNA detection compared to SEC. Furthermore, the research proposes that immunoaffinity capture enriched EVs can function as biomarkers for periodontitis, demonstrated by an increased expression of proinflammatory cytokines from periodontitis patients.

Project description:Extracellular RNA in circulation mediates intercellular communication in normal and pathological processes. One mode of circulating miRNA transport in bodily fluids is within 30-150 nm small extracellular vesicles (sEVs) or exosomes. Uptake of sEVs can regulate gene expression in recipient cells enabling circulating miRNAs to exert paracrine and systemic effects. Complex regional pain syndrome (CRPS) is a debilitating pain disorder characterized by chronic inflammation. Our previous investigations identified a significant decrease of hsa-miR-939 in whole blood from CRPS patients compared to control; we also observed that overexpression of miR-939 can negatively regulate several proinflammatory genes in vitro. Though downregulated in whole blood, miR-939 was significantly upregulated in sEVs isolated from patient serum. Here we investigated miR-939 packaging into sEVs in vitro under inflammation induced by monocyte chemoattractant protein-1 (MCP-1), a chemokine that is upregulated in CRPS patients. Stimulation of THP-1 monocytes by MCP-1 led to elevated levels of miR-939 in sEVs, which was abrogated using inhibitors of exosome secretion. miRNAs loaded into exosomes largely contain short miRNA sequence motifs called EXOmotifs. Mutation analysis of miR-939 showed that EXOmotif is one of the possible cellular mechanisms responsible for packaging miR-939 into sEVs. We confirmed gene expression changes in recipient cells following the uptake of sEVs enriched in miR-939 using RNA sequencing. Additionally, our data from primary immune cell-derived sEVs of CRPS patients and controls demonstrate that while the relative expression of miR-939 is higher in sEVs derived from B cells, T cells and NK cells relative to monocyte-derived sEVs in controls, only the B cell-derived sEVs showed a significantly higher level of miR-939 in CRPS patients. Differential miRNA sorting into exosomes and its functional impact on recipient cells may contribute to the underlying pathophysiology of CRPS.

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Inflammation-related gene expression profiles of salivary extracellular vesicles in patients with head trauma.

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Inflammation-related gene expression profiles of salivary extracellular vesicles in patients with head trauma.

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