The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Evidence for Epigenetic Regulation of Pro-Inflammatory Cytokines, Interleukin-12 and Interferon Gamma, in Peripheral Blood Mononuclear Cells from PTSD Patients
Open accessAbstract
While Post Traumatic Stress Disorder (PTSD) is associated with immune dysfunction, the underlying mechanisms remain unclear. Studies suggest a role for involvement of epigenetic mechanisms and microRNAs (miRNAs). Here, we examined genome-wide histone and DNA methylation in the peripheral blood mononuclear cells (PBMCs) in PTSD. We noted significant differences in histone H3 trimethylation at K4, K9, K27 and K36 sites in PTSD when compared to control. While overall DNA methylation level did not differ significantly between control and PTSD, the promoters of several individual genes (e.g., Interferon gamma (IFNG) and Interleukin (IL)-12B) were differentially methylated. ChIP-seq data revealed that the promoter of IFNG and TBX-21 was associated with the activation marker H3K4me3 in PTSD. The transcript levels of both IFNG and TBX-21 were higher in PTSD correlating well with the altered methylation patterns. Furthermore, PTSD patients showed increased expression of IL-12 in their PBMCs. Analysis of both histone and DNA methylation markers suggested that the expression of IL-12 was also possibly activated through epigenetic modification. Knockdown of lysine (K)-specific demethylase 5B (KDM5B), or inhibition of DNA (Cytosine-5-)-methyltransferase 1 (DNMT1) caused up-regulation of IL-12. Furthermore, the expression of these cytokines was also regulated by miRNAs. Our miRNA microarray identified many downregulated miRNAs in PTSD that are predicted to target IFNG and IL-12. Consequently, we showed that up-regulation of hsa-miR-193a-5p could decrease the expression of IL-12. Overall, the current study demonstrated that the elevated expression of pro-inflammatory cytokines in PTSD patients might be regulated by multiple epigenetic mechanisms and miRNAs.
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“Further human PTSD research suggested that elevated expression of pro-inflammatory cytokines after traumatic stress exposure is probably regulated by multiple epigenetic mechanisms, including dysregulation of microRNA expression (216–218).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [218]
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Epigenetic mechnisms involved in posttraumatic stress disorder
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Metadata
- Authors
- Bam, M., Yang, X., Zhou, J., Ginsberg, J. P., Leyden, Q., Nagarkatti, P. S., & Nagarkatti, M.
- Affiliations
- University of South Carolina (US)
- Wm. Jennings Bryan Dorn VA Medical Center (US)
- Corresponding author
- Nagarkatti, Mitzi
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2015-11-20
- Volume
- 11
- Issue
- 1
- Pages
- 168-181
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- PMC
- PMC4746110
- OpenAlex
- W2220459051
- Semantic Scholar
- dc2f2acbce072f1d6ccac7dfe3c7d8b1b0b7cb79
- Cited by
- 103
- References
- 48
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 11 · 2023: 7 · 2022: 14 · 2021: 17 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 6
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P01AT003961, R01AT006888, R01ES019313, R01MH094755, and P20GM103641)
- U.S. Department of Veterans Affairs (BX001357)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- post-traumatic stress disorder, epigenetic regulation, histone methylation, DNA methylation, IL-12, interferon-gamma, TBX21, inflammatory cytokines, microRNA, KDM5B, DNMT1, H3K4me3, peripheral blood mononuclear cells, immune dysfunction
- MeSH terms
- Acetylcysteine, Adult, Female, Gene Expression Regulation, Humans, Interferon-gamma, Leukocytes, Mononuclear, Male, Promoter Regions, Genetic, Stress Disorders, Post-Traumatic, Transfection, Cytokines, Interleukin-12, DNA Methylation, Epigenesis, Genetic, Chromatin Immunoprecipitation, Gene Knockdown Techniques, Real-Time Polymerase Chain Reaction
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