scholarly journals Identification of the Transcription Factors of CD200R1 and Its Potential Roles in Parkinson’s Disease

2021 ◽  
Author(s):  
Suzhen Lin ◽  
Ruinan Shen ◽  
Hong Pan ◽  
Lu He ◽  
Fang Fang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Promoter Region ◽  
Mononuclear Cells ◽  
Core Promoter ◽  
Core Promoter Region ◽  
Peripheral Blood Mononuclear ◽  
The Core ◽  
Blood Mononuclear Cells

Abstract BackgroundNeuroinflammation is known to be involved in the pathogenesis of Parkinson's disease (PD). Abnormal activation of microglia plays a key role in this pathological process. CD200R1 is a membrane glycoprotein primarily expressed in microglia in central nervous system responsible for transducing signaling maintaining microglia in stationary status. Our previous studies have demonstrated the dysregulation of CD200R1 and its involvement in PD pathogenesis. The binding of transcription factors with promoter regions is the basic and essential step for the regulation of gene expression. However, little is known about the human CD200R1 promoter region and the mechanism of the dysregulated expression of CD200R1 in PD. MethodsLuciferase reporter system was initially employed to identify the core region of CD200R1 promoter and figure out its potential transcription factors. Subsequently, we investigated the interaction adopting electrophoretic mobility shift assay and chromatin immunoprecipitation assay. The regulatory function of the detected transcription factors were further proved through its down-regulation and overexpression. We then collected the peripheral blood mononuclear cells from both PD patients and their healthy counterparts with matched age and sex to evaluate whether consistent results existed under clinical setting. Ultimately, the mouse model was established through knocking-out the identified transcription factor and its role in neuroinflammation and pathogenesis of PD was explored. ResultsWe defined that the core promoter region of CD200R was located within -482 to -146 bp upstream of the translation initiation site (TIS). In addition, we demonstrated that NFKB1 directly bound to the CD200R1 core promoter region and regulated its transcriptional activity. Besides, the expression of NFKB1 and CD200R1 was significantly correlated in human peripheral blood mononuclear cells and knocking down NFKB1 significantly reduced CD200R1 expression. Moreover, both NFKB1 and CD200R1 were significantly downregulated in samples from PD patients. Furthermore, NFKB1-/- mice exhibited exacerbated microglia activation and dopaminergic neuron loss after MPTP treatment. ConclusionOur study provided novel understanding of the transcriptional regulation of CD200R1 and its role in microglia homeostasis in the pathogenesis of PD.

Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells

1995 ◽  
Vol 268 (2) ◽  
pp. C331-C338 ◽  
Author(s):  
I. M. Adcock ◽  
C. R. Brown ◽  
C. M. Gelder ◽  
H. Shirasaki ◽  
M. J. Peters ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Nf Kappa B ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Glucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA. The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF kappa B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays. TNF-alpha, IL-1 beta and phorbol myristate acetate (PMA) treatment increased AP-1 and NF kappa B DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course. Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF kappa B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment. These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors. This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling. This may be an important molecular site of steroid action.

scholarly journals Integrated Analysis of mRNA and Long Noncoding RNA Profiles in Peripheral Blood Mononuclear Cells of Patients with Bronchial Asthma

2021 ◽  
Author(s):  
Han Cui ◽  
Ruirui Duan ◽  
Hongtao Niu ◽  
Tao Yu ◽  
Ke Huang ◽  
...  
Keyword(s):  
Bronchial Asthma ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interaction Network ◽  
Functional Interaction ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
The Core ◽  
Blood Mononuclear Cells

Abstract Background: Bronchial asthma is a heterogeneous disease with distinct disease phenotypes and underlying pathophysiological mechanisms. Long non-coding RNAs (lncRNAs) are involved in numerous functionally different biological and physiological processes. The aim of this study was to identify differentially expressed lncRNAs and mRNAs in patients with asthma and further explore the functions and interactions between lncRNAs and mRNAs.Methods: Ten patients with asthma and 9 healthy controls were enrolled in this study. RNA was isolated from peripheral blood mononuclear cells. We performed microarray analysis to evaluate lncRNA and mRNA expression. The functions of the differentially expressed mRNAs were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. A global signal transduction network was constructed to identify the core mRNAs. An lncRNA–mRNA network was constructed. Five mRNAs showing the greatest differences in expression levels or high degrees in the gene-gene functional interaction network, with their correlated lncRNAs, were validated by real-time quantitative polymerase chain reaction. Results: We identified 2,229 mRNAs and 1,397 lncRNAs between the asthma and control groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified many pathways associated with inflammation and cell survival. The gene-gene functional interaction network suggested that some core mRNAs are involved in the pathogenesis of bronchial asthma. The lncRNA–mRNA co-expression network revealed correlated lncRNAs. CXCL8, FOXO3, JUN, PIK3CA, and G0S2 and their related lncRNAs NONHSAT115963, AC019050.1, MTCYBP3, KB-67B5.12, and HNRNPA1P12 were identified according to their differential expression levels and high degrees in the gene-gene network. Conclusions: We identified the core mRNAs and their related lncRNAs and predicted the biological processes and signaling pathways involved in asthma.

scholarly journals Molecular signatures of peripheral blood mononuclear cells during chronic interferon-α treatment: relationship with depression and fatigue

2011 ◽  
Vol 42 (8) ◽  
pp. 1591-1603 ◽  
Author(s):  
J. C. Felger ◽  
S. W. Cole ◽  
T. W. W. Pace ◽  
F. Hu ◽  
B. J. Woolwine ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Major Depression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Myeloid Differentiation ◽  
Oligoadenylate Synthetase ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
The Impact

BackgroundInterferon-alpha (IFN-α) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-α on immune cellsin vivoand its relationship to IFN-α-induced behavioral changes.MethodGenome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-α therapy (n=10) or at 12 weeks of IFN-α treatment (n=11).ResultsSignificance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2′-5′-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-α-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80,p=0.003 andr=0.70,p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-α-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-α signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-α-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-α and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression.ConclusionsDepression and fatigue during chronic IFN-α administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

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