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BRIEF RESEARCH REPORT article

Front. Psychiatry
Sec. Anxiety and Stress Disorders
Volume 15 - 2024 | doi: 10.3389/fpsyt.2024.1436690
This article is part of the Research Topic Molecular Mechanisms in Psychiatry 2023: Anxiety and Stress View all 3 articles

FLI1 in PBMCs contributes to elevated inflammation in combat-related posttraumatic stress disorder

Provisionally accepted
Pengfei Li Pengfei Li 1,2Liu Liu Liu Liu 1Shufeng Liu Shufeng Liu 3Zhongyang Lu Zhongyang Lu 2Perry V. Halushka Perry V. Halushka 4Sara J. Sidles Sara J. Sidles 1,2Amanda C. LaRue Amanda C. LaRue 1,2Zhewu Wang Zhewu Wang 2,3Hongkuan Fan Hongkuan Fan 1*
  • 1 Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, United States
  • 2 Ralph H. Johnson VA Medical Center, United States Department of Veterans Affairs, Charleston, South Carolina, United States
  • 3 Department of Psychiatry, Medical University of South Carolina, Charleston, United States
  • 4 Department of Pharmacology, Medicine, Medical University of South Carolina, Charleston, United States

The final, formatted version of the article will be published soon.

    Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with significant public health implications that arise following exposure to traumatic events.Recent studies highlight the involvement of immune dysregulation in PTSD, characterized by elevated inflammatory markers. However, the precise mechanisms underlying this immune imbalance remain unclear. Previous research has implicated friend leukemia virus integration 1 (FLI1), an erythroblast transformation-specific (ETS) transcription factor, in inflammatory responses in sepsis and Alzheimer's disease. Elevated FLI1 levels in peripheral blood mononuclear cells (PBMCs) have been linked to lupus severity. Yet, FLI1's role in PTSD-related inflammation remains unexplored. In our study, PBMCs were collected from Veterans with and without PTSD. We found significantly increased FLI1 expression in PBMCs from PTSD-afflicted Veterans, particularly in CD4 + T cells, with no notable changes in CD8 + T cells. Stimulation with LPS led to heightened FLI1 expression and elevated levels of inflammatory cytokines IL-6 and IFNγ in PTSD PBMCs compared to controls. Knockdown of FLI1 using Gapmers in PTSD PBMCs resulted in a marked reduction in inflammatory cytokine levels, restoring them to control group levels.Additionally, co-culturing PBMCs from both control and PTSD Veterans with the human brain microglia cell line HMC3 revealed increased inflammatory mediator levels in HMC3.Remarkably, HMC3 cells co-cultured with PTSD PBMCs treated with FLI1 Gapmers exhibited significantly lower inflammatory mediator levels compared to control Gapmertreated PTSD PBMCs. These findings suggest that suppressing FLI1 may rebalance immune activity in PBMCs and mitigate microglial activation in the brain. Such insights could provide novel therapeutic strategies for PTSD.

    Keywords: FLI1, Inflammation, PTSD, PBMC, antisense oligonucleotides

    Received: 22 May 2024; Accepted: 05 Jul 2024.

    Copyright: © 2024 Li, Liu, Liu, Lu, Halushka, Sidles, LaRue, Wang and Fan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hongkuan Fan, Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.