Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation

Bam, Marpe; Yang, Xiaoming; Zumbrun, Elizabeth E.; Ginsberg, J. P.; Leyden, Quinne; Zhang, J; Nagarkatti, Mitzi

doi:10.1038/tp.2017.185

Cited by 24 publications

(12 citation statements)

References 59 publications

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“…Circulating blood monocytes are also precursors of macrophages. Activated macrophages and monocytes have been proposed to play a major role in pathogenesis of several central nervous system conditions and neurological disorders as well as PTSD 55,56 . Practically, these results suggest that future PTSD studies that wish to focus on gene expression in an isolated cell type might benefit from focusing on monocytes.…”

Section: Discussionmentioning

confidence: 99%

Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders

Kuan

Yang

Clouston³

et al. 2019

Transl Psychiatry

236

187

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Posttraumatic stress disorder (PTSD), a chronic disorder resulting from severe trauma, has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene expression of four immune cell subpopulations (CD4T, CD8T, B cells, and monocytes) in 39 World Trade Center responders (20 with and 19 without PTSD) to determine which immune subsets play a role in the transcriptomic changes found in whole blood. Transcriptome-wide analyses identified cell-specific and shared differentially expressed genes across the four cell types. FKBP5 and PI4KAP1 genes were consistently upregulated across all cell types. Notably, REST and SEPT4, genes linked to neurodegeneration, were among the top differentially expressed genes in monocytes. Pathway analyses identified differentially expressed gene sets involved in mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil-related gene sets in monocytes. These findings suggest that gene expression indicative of immune dysregulation is common across several immune cell populations in PTSD. Furthermore, given notable differences between cell subpopulations in gene expression associated with PTSD, the results also indicate that it may be valuable to analyze different cell populations separately. Monocytes may constitute a key cell type to target in research on gene expression profile of PTSD.

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Section: Discussionmentioning

confidence: 99%

Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders

Kuan

Yang

Clouston³

et al. 2019

Transl Psychiatry

236

187

View full text Add to dashboard Cite

show abstract

“…Recent work has suggested an emerging role for transposable element RNA in regulating local inflammatory responses and housekeeping gene expression ( Allen et al, 2004 ; Espinoza et al, 2004 ; Yakovchuk et al, 2009 ; Kaneko et al, 2011 ; Tarallo et al, 2012 ). In the former context, accumulation of Alu retrotransposon RNA following DICER1 loss of function facilitated NLRP3 inflammasome activation and subsequent macular degeneration ( Tarallo et al, 2012 ; Bam et al, 2017 ). Interestingly, DICER loss of function has been associated with increased inflammation and PTSD diagnosis and also has been shown to be predictive of PTSD status comorbid with depression ( Bam et al, 2017 ; Wingo et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Corticosterone dynamically regulates retrotransposable element expression in the rat hippocampus and C6 cells

Bartlett

DeRosa

Clark

et al. 2021

Neurobiology of Stress

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The hippocampus is a highly plastic brain region sensitive to environmental stress. It shows dynamic changes in epigenetic marks associated with stress related learning. Previous work has shown that acute stress induces substantial transient changes in histone H3 lysine 9 trimethylation (H3K9me3). Moreover, increased H3K9me3 is enriched in hippocampal gene deserts accumulating within endogenous retroviruses and transposable elements. We have found that in response to acute glucocorticoid treatment, a similar change in global H3K9me3 is observed. However, when localized we found that H3K9me3 is markedly decreased at B2 short interspersed nuclear elements but not within intracisternal-A particle endogenous retroviruses. Further, decreased H3K9me3 valence within B2 elements was associated with increased transcript abundance. These data demonstrate the capacity for acute glucocorticoids to mobilize transposable elements via epigenetic unmasking. Reconciled with previous findings following acute stress, this suggests the capacity for mobile elements to potentially function as novel regulators given their dynamic regulation by stress and glucocorticoids.

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“…The microarray was performed at the University of South Carolina School of Medicine following the protocol described by Bam et al[ 36 , 37 ]. Briefly, total RNA isolated as described above was hybridized to an Affymetrix miRNA-v3 gene chip (Affymetrix, Sunnyvale, CA, United States) as directed by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

Immune and microRNA responses toHelicobacter muridaruminfection and indole-3-carbinol during colitis

Alkarkoushi

Hui

Tavakoli

et al. 2020

WJG

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BACKGROUND Indole-3-carbinol (I3C) and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models, including colitis induced by dextran sulfate sodium (DSS). MicroRNAs (miRNAs) are also gaining traction as potential therapeutic agents or diagnostic elements. Enterohepatic Helicobacter (EHH) species are associated with an increased risk of inflammatory bowel disease, but little is known about how these species affect the immune system or response to treatment. AIM To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH species compare with responses to DSS and inflammatory bowel disease. METHODS We infected C57BL/6 mice with Helicobacter muridarum ( H. muridarum ), with and without DSS and I3C treatment. Pathological responses were evaluated by histological examination, symptom scores, and cytokine responses. MiRNAs analysis was performed on mesenteric lymph nodes to further evaluate the regional immune response. RESULTS H. muridarum infection alone caused colonic inflammation and upregulated proinflammatory, macrophage-associated cytokines in the colon similar to changes seen in DSS-treated mice. Further upregulation occurred upon treatment with DSS. H. muridarum infection caused broad changes in mesenteric lymph node miRNA expression, but colitis-associated miRNAs were regulated similarly in H. muridarum- infected and uninfected, DSS-treated mice. In spite of causing colitis exacerbation, H. muridarum infection did not prevent disease amelioration by I3C. I3C normalized both macrophage- and T cell-associated cytokines. CONCLUSION Thus, I3C may be useful for inflammatory bowel disease patients regardless of EHH infection. The miRNA changes associated with I3C treatment are likely the result of, rather than the cause of immune response changes.

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Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation

Cited by 24 publications

References 59 publications

Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders

Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders

Corticosterone dynamically regulates retrotransposable element expression in the rat hippocampus and C6 cells

Immune and microRNA responses toHelicobacter muridaruminfection and indole-3-carbinol during colitis

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