miR-155 In Peripheral Blood Mononuclear Cells Research Articles

Aberrant Histone Modification of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in Major Depressive Disorder.

Activated toll-like receptor (TLR) signaling has been well investigated in major depressive disorder (MDD). We previously reported that TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 play important roles in regulating the toll-like receptor 4 (TLR4) signaling pathway and may serve as novel targets in the pathogenesis of MDD. Recently, aberrant histone modification has been implicated in several psychiatric disorders, including schizophrenia and mood disorder; the most thoroughly studied modification is histone 3 lysine 4 tri-methylation (H3K4me3). In this work, we aimed to explore H3K4me3 differences in the promotors of genes encoding the abovementioned factors in patients with MDD, and whether they were altered after antidepressant treatment. A total of 30 MDD patients and 28 healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were collected. The levels of H3K4me3 in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 were measured through chromatin immunoprecipitation (ChIP) followed by DNA methylation assay. Analysis of covariance was used to evaluate between-group differences after adjusting for age, sex, BMI, and smoking. In comparison with healthy controls, patients with MDD showed significantly lower H3K4me3 levels in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in PBMCs. These levels were not significantly altered after completion of a 4-week antidepressant treatment. To explore the association between depression severity and H3K4me3 levels, a multiple linear regression model was generated. The results revealed that levels of H3K4me3 in the TNIP2 promoters a negative correlation with the 17-item Hamilton Depression Rating Scale (HAND-17) score, whereas that of TLR4 had a positive correlation with this score. The present results suggest that decreased H3K4me3 levels in the promoters of the genes encoding TNFAIP3, TLR4, miR-146a, miR-155, and TNIP2 are involved in psychopathology of major depressive disorder.

MiR-155 rs767649 T>A gene polymorphism is associated with downregulation of miR-155 expression, suppressor of cytokine signaling-1 overexpression, and low probability of metastatic tumor at the time of breast cancer diagnosis.

MicroRNA-155 is a key player in inflammatory reactions, carcinogenesis, and tumor development. In this study, polymorphism of miRNA-155 rs767649 T>A and its gene and suppressor of cytokine signaling-1 (SOCS-1) expression were investigated in relation to cancer susceptibility and development in breast cancer (BC) patients. Polymorphism of miRNA-155 rs767649 T>A was evaluated between a population of 174 patients with BC and 129 controls using restriction fragment length polymorphism and the expression of miR-155 and SOCS-1 were examined in peripheral blood mononuclear cells (PBMCs) by real-time polymerase chain reaction. TT genotype of miR-155 rs767649 T>A was associated with higher level of miR-155 in PBMCs of BC patients relative to AT and AA genotypes (21.76 ± 4.4, 4.046 ± 1.35, 2.56 ± 0.81, respectively; P < 0.001) and increased lymph node metastasis (r = 0.292, P = 0.001), not BC susceptibility (P = 0.402 and P = 0.535; respectively). TT genotype of miR-155 rs767649 T>A was associated with less gene expression of SOCS-1 in PBMCs of BC patients compared to AT and AA genotypes (1.173 ± 0.57, 0.92 ± 0.827, 5.512 ± 0.92, respectively; P = 0.003). This study demonstrated for the first time the association between the T allele of the rs767649 T>A polymorphism in the pre-MIR155 gene and higher expression of miR-155, lower expression of SOCS-1, and swift latent progression in newly diagnosed BC patients. Thus, miR-155 may play a critical role in BC pathogenesis.

Revisiting miR-155 in intervertebral disc degeneration: blood cell signature and local cell-free profiles

We unraveled the expression profiles of coding-noncoding RNAs in intervertebral disc degeneration (IDD). However, it remains elusive regarding miR-155 expression in peripheral blood mononuclear cells (PBMCs) and local extracellular space in IDD. The study aimed for investigating the miR-155 expression of PBMCs, extracellular miRNAs (ex-miRNAs) of human nucleus pulposus (NP) tissues, and morphological changes of cell death in the IDD process. Here, we harvested peripheral blood and NP samples from scoliosis and IDD patients as control and degenerative groups, respectively. Then standard Ficoll density-gradient centrifugation was used to isolate PBMCs. The two subpopulations of PBMCs were divided based on the cellular difference in adherence, i.e., monocytes/ macrophages and lymphocytes. Quantitative real-time PCR was used to evaluate miR-155 relative expression in PBMCs. ex-miRNAs were screened by comparison between GSE19943, GSE63492, and extracellular RNA (exRNA) atlas. The morphological changes of cell death subtypes in IDD were observed in transmission electron microscopy (TEM). Results indicate that the lower expression of miR-155 in PBMCs from IDD patients ascribed to alterations in monocytes/macrophages. Moreover, we identified 594 shared hsa-miRNAs as the intracellular miRNA expression profile and 258 miRNAs as the ex-miRNA expression profile in human NP tissue. miR-155 was amongst intracellular miRNAs in NP. TEM observation presented multiple endocytic secretory vesicles within human NP cells, implicating exosome transporting machinery. Typical necroptosis and pyroptosis were noted in human NP. Collectively, this study reveals miR-155 expression in PBMCs from IDD patients. Moreover, we propose ex-miRNA expression profile and necroptosis/pyroptosis in human NP tissue, shedding novel light on the etiology of IDD.

Revisiting miR-155 in intervertebral disc degeneration: blood cell signature and local cell-free profiles

We unraveled the expression profiles of coding-noncoding RNAs in intervertebral disc degeneration (IDD). However, it remains elusive regarding miR-155 expression in peripheral blood mononuclear cells (PBMCs) and local extracellular space in IDD. The study aimed for investigating the miR-155 expression of PBMCs, extracellular miRNAs (ex-miRNAs) of human nucleus pulposus (NP) tissues, and morphological changes of cell death in the IDD process. Here, we harvested peripheral blood and NP samples from scoliosis and IDD patients as control and degenerative groups, respectively. Then standard Ficoll density-gradient centrifugation was used to isolate PBMCs. The two subpopulations of PBMCs were divided based on the cellular difference in adherence, i.e., monocytes/ macrophages and lymphocytes. Quantitative real-time PCR was used to evaluate miR-155 relative expression in PBMCs. ex-miRNAs were screened by comparison between GSE19943, GSE63492, and extracellular RNA (exRNA) atlas. The morphological changes of cell death subtypes in IDD were observed in transmission electron microscopy (TEM). Results indicate that the lower expression of miR-155 in PBMCs from IDD patients ascribed to alterations in monocytes/macrophages. Moreover, we identified 594 shared hsa-miRNAs as the intracellular miRNA expression profile and 258 miRNAs as the ex-miRNA expression profile in human NP tissue. miR-155 was amongst intracellular miRNAs in NP. TEM observation presented multiple endocytic secretory vesicles within human NP cells, implicating exosome transporting machinery. Typical necroptosis and pyroptosis were noted in human NP. Collectively, this study reveals miR-155 expression in PBMCs from IDD patients. Moreover, we propose ex-miRNA expression profile and necroptosis/pyroptosis in human NP tissue, shedding novel light on the etiology of IDD.

Value of MiR-155 in Prognostic Evaluation of Elderly Patients with Primary Immune Thrombocytopenia

To explore the value of has-microRNA-155 (miR-155) in peripheral blood mononuclear cells (PBMNC) in prognostic evaluation of elderly patients with primary immune thrombocytopenia (PITP). One hundred and thirty elderly PITP patients and 60 healthy volunteers in our hospital were selected. The relative expression level of miR-155 in PBMNC was detected by RT-PCR. Unconditional logistic multivariate regression analysis was used to analyze the relationship between miR-155 expression and prognosis of PITP patients, and Kaplan-Meier was further used to analyze the relationship between miR-155 and PITP recurrence. The relative expression level of miR-155 in PBMNC of elderly PITP patients was significantly higher than that in healthy volunteers, and increased significantly with the severity of the disease (P＜0.05). The overall effective rate of elderly PITP patients with miR-155 low-expression was significantly higher than that in the patients with miR-155 high-expression (96.92% vs 72.31%) by after treatment with glucocorticoid. Multivariate analysis showed that miR-155 was an independent risk factor for PITP patients. Elderly patients with high expression of miR-155 showed a higher risk of recurrence. miR-155 in PBMNC has a high accuracy for PITP diagnosis, and the elderly patients with high level of miR-155 show a poor prognosis and a higher risk of recurrence.

Inflammation-Related MicroRNAs Are Associated with Plaque Stability Calculated by IVUS in Coronary Heart Disease Patients.

Objectives This study aimed to investigate the association between inflammation-related microRNAs (miR-21, 146a, 155) and the plaque stability in coronary artery disease patients. Methods The expression of miR-21, 146a, and 155 was measured by real-time PCR in 310 consecutive patients. The level of hs-CRP, IL-6, and IL-8 was measured by ELISA. The plaque stability of coronary stenotic lesions was evaluated with intravascular ultrasound (IVUS). Results (1) The levels of hs-CRP, IL-6, and IL-8 were significantly increased in the UAP and AMI groups compared with the CPS group (P < 0.01). (2) The expression of miR-21 and miR-146a in peripheral blood mononuclear cells (PBMCs) and plasma was significantly higher in CAD patients compared with non-CAD patients, whereas the miR-155 expression in PBMCs and plasma was significantly lower in patients with CAD. (3) The miR-21 expression in PBMCs was higher in UAP and AMI groups compared with CPS group. The miR-146a expression in PBMCs was higher in SAP, UAP, and AMI groups than in CPS group. Although the level of miR-155 in PBMCs was lower in SAP, UAP, and AMI groups than in CPS group. The expression patterns of miR-21, miR-146a, and miR-155 in plasma were consistent with those of PBMCs. (4) The expressions of miR-21 and miR-146a in PBMCs and plasma were significantly higher in the vulnerable plaque group than those in stable plaque group. While miR-155 in PBMCs and plasma was significantly lower in vulnerable plaque group compared with stable plaque group. (5) The levels of miR-21 and miR-146a in PBMCs and plasma were significantly higher in soft plaque group than in fibrous plaque group and calcified plaque group. However, miR-155 in PBMCs and plasma was significantly lower in soft plaque group. Conclusions The expression of miR-21 and miR-146a are associated with the plaque stability in coronary stenotic lesions, whereas miR-155 expression is inversely associated with the plaque stability.

Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring.

It was previously demonstrated that non-allergen-sensitized rodents born to mothers exposed to a high-fat diet (HFD) spontaneously develop lower respiratory compliance and higher respiratory resistance. In the present study, we sought to determine if mice born to mothers consuming HFD would exhibit changes in inflammatory response and lung remodeling when subjected to ovalbumin (OVA) sensitization/challenge in adult life. Mice born to dams consuming either HFD or standard chow had increased bronchoalveolar lavage (BAL) levels of IL-1β, IL-4, IL-5, IL-10, IL-13, TNF-α and TGF-β1 after challenge with OVA. IL-4, IL-13, TNF-α and TGF-β1 levels were further increased in the offspring of HFD-fed mothers. Mice born to obese dams also had exacerbated values of leukocyte infiltration in lung parenchyma, eosinophil and neutrophil counts in BAL, mucus overproduction and collagen deposition. The programming induced by maternal obesity was accompanied by increased expression of miR-155 in peripheral-blood mononuclear cells and reduced miR-133b in trachea and lung tissue in adult life. Altogether, the present data support the unprecedented notion that the progeny of obese mice display exacerbated responses to sensitization/challenge with OVA, leading to the intensification of the morphological changes of lung remodeling. Such changes are likely to result from long-lasting changes in miR-155 and miR-133b expression.

Elevated expression of miR-21 and miR-155 in peripheral blood mononuclear cells as potential biomarkers for lupus nephritis.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). There is a great interest in using microRNAs (miRNAs) as diagnostic and prognostic biomarkers in autoimmune diseases. This study evaluated miR-16, miR-21, miR-141, miR-146a, and miR-155 expression levels in peripheral blood mononuclear cells (PBMCs) of 55 female SLE patients with absent, inactive, or active nephritis, and 30 healthy controls (HCs) using quantitative polymerase chain reaction. MiR-21 and miR-155 levels were significantly greater in the active nephritis group than in the absent, inactive or HC groups. Moreover, receiver operating characteristic and logistic regression analyses revealed miR-21 and miR-155 were significant risk factors for LN. Overexpression of miR-21 and miR-155 in PBMCs may participate in LN pathophysiology and these miRNAs could be used as biomarkers for the condition.

Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus.

IntroductionInterleukin (IL)-21 is a key cytokine in autoimmune diseases such as systemic lupus erythematosus (SLE) by its regulation of autoantibody production and inflammatory responses. The objective of this study is to investigate the signaling capacity of IL-21 in T and B cells and assess its possible regulation by microRNA (miR)-155 and its target gene suppressor of cytokine signaling 1 (SOCS1) in SLE.MethodsThe signaling capacity of IL-21 was quantified by stimulating peripheral blood mononuclear cells (PBMCs) with IL-21 and measuring phosphorylation of STAT3 (pSTAT3) in CD4+ T cells, B cells, and natural killer cells. Induction of miR-155 by IL-21 was investigated by stimulating purified CD4+ T cells with IL-21 and measuring miR-155 expression levels. The functional role of miR-155 was assessed by overexpressing miR-155 in PBMCs from SLE patients and healthy controls (HCs) and measuring its effects on STAT3 and IL-21 production in CD4+ and CD8+ T cells.ResultsInduction of pSTAT3 in CD4+ T cells in response to IL-21 was significantly decreased in SLE patients compared to HCs (p < 0.0001). Further, expression levels of miR-155 were significantly decreased and SOCS1 correspondingly increased in CD4+ T cells from SLE patients. Finally, overexpression of miR-155 in CD4+ T cells increased STAT3 phosphorylation in response to IL-21 treatment (p < 0.01) and differentially increased IL-21 production in SLE patients compared to HCs (p < 0.01).ConclusionWe demonstrate that SLE patients have reduced IL-21 signaling capacity, decreased miR-155 levels, and increased SOCS1 levels compared to HCs. The reduced IL-21 signaling in SLE could be rescued by overexpression of miR-155, suggesting an important role for miR-155 in the reduced IL-21 signaling observed in SLE.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0660-z) contains supplementary material, which is available to authorized users.

Expression level of miR-155 in peripheral blood.

To investigate the relationship between the expression level of miR-155 and the severity of coronary lesion, and explore the action mechanism. Peripheral blood mononuclear cells (PBMC) were isolated form blood simple from patients with acute myocardial infarction (AMI), unstable angina (UAP), stable angina (SAP) and chest pain syndrome (CPS). RT-PCR was performed to analysis the expression level of miR-155 in peripheral blood mononuclear cells, plasma and RAW264.7 macrophagocyte. MTT was used to analyze the cell viability of OxLDL treated RAW264.7 macrophagocyte. The expression level of miR-155 in blood sample from coronary heart disease patients was much lower than in the blood sample of non-coronary heart disease (P<0.05). The level of miR-155 in PBMCs was much higher in the blood sample from CPS group than the other three group, and the level of miR-155 in plasma was higher in the CPS group than in the UAP and the AMI group, the difference was statistically significant (P<0.05). The expression level of miR-155 in PBMCs is positively associated with the level in the plasma (r=0.861, P=0.000). OxLDL can induce the expression of miR-155 in RAW264.7 macrophagocyte, decrease the cell viability of RAW264.7 macrophagocyte, and with the concentration and the treatment time of OxLDL increased, the effort become more obvious. The inhibition effort of OxLDL to RAW264.7 macrophagocyte with high miR-155 expression is much lower than the control group, and it is statistically significant after treated for 12, 24 and 48 h. miR-155 plays a protective role in the progression of atherosclerosis, and it may be achieved by reducing the apoptosis effort of OxLDL to RAW264.7 macrophagocyte.

Silencing of miR155 Promotes the Production of Inflammatory Mediators in Guillain–Barré Syndrome In Vitro

MicroRNA-155 (miR155) has been demonstrated as a central regulator of immune responses induced by inflammatory mediators. Previous studies suggest that miR155 may play adverse effects in various diseases. We hereby explored the roles of miR155 in the pathogenesis of Guillain-Barré syndrome (GBS). Peripheral blood mononuclear cells (PBMCs) were separated from GBS patients and healthy controls. Expression of miR155 in PBMCs was detected by quantitative PCR. An inhibitor of miR155 was transfected into the cultured PBMCs and the GBS-related cytokines were detected. Significantly, our study demonstrated that miR155 was downregulated in PBMCs from GBS patients and silencing of miR155 profoundly promoted the production of Th1-type cytokines in vitro. Our data effectively demonstrate a protective role of miR155 in GBS, which suggests that miR155 may be a promising target for the therapy of the disease.