Inhibitory effects of miR‑25 targeting HMGB1 on macrophage secretion of inflammatory cytokines in sepsis

Zhu,Chunyan; Chen,Ting; Liu,Bao

doi:10.3892/ol.2018.9308

Inhibitory effects of miR‑25 targeting HMGB1 on macrophage secretion of inflammatory cytokines in sepsis

Authors:
- Chunyan Zhu
- Ting Chen
- Bao Liu
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Affiliations: Intensive Care Unit, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui 230032, P.R. China, Intensive Care Unit, The Second People's Hospital of Hefei, Hefei, Anhui 230032, P.R. China
Published online on: August 14, 2018 https://doi.org/10.3892/ol.2018.9308
Pages: 5027-5033
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

High mobility group box 1 (HMGB1) can promote the migration of macrophages and the release of inflammatory cytokines, functions associated with the occurrence of sepsis. The role of microRNA (miR)‑25 in the targeted regulation of HMGB1 expression and the release of macrophage inflammatory cytokines remains uncharacterized. The present study investigated the association between miR‑25, HMGB1 and sepsis by analyzing the expression of miR‑25 and HMGB1 in patients with sepsis. The present study also investigated whether miR‑25 serves a role in targeting the regulation of HMGB1 expression and macrophage inflammatory factor release. Patients with sepsis were selected from the Intensive Care Unit, and serum levels of HMGB1. The expression of miR‑25 and HMGB1 in serum and peripheral blood mononuclear cells (PBMCs) was compared. Macrophages were cultured in vitro and divided into 5 groups following treatment with lipopolysaccharide (LPS). The expression levels of miR‑25, HMGB1, phosphorylated (p‑)p65, tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6) and HMGB‑1 were compared, and the migration ability of cells was investigated by Transwell assays. Compared with the healthy controls, patients with sepsis exhibited elevated expression of HMGB1 and decreased expression of miR‑25 in serum and PBMCs. Following treatment with LPS, the expression of HMGB1 and p‑p65 was elevated, and the expression of miR‑25 was decreased in macrophages compared with untreated cells. Following transfection with miR‑25 mimics and/or short interfering RNA‑HMGB1, the expression of HMGB1 in macrophages decreased significantly, the expression of p‑p65, HMGB‑1, TNF‑α and IL‑6 in the culture solution were also decreased, and the migration ability of macrophages was attenuated. The present study suggests that miR‑25 attenuated the induction of HMGB1 by LPS, decreased the activity of nuclear factor‑κB and the transcriptional activation of TNF‑α and IL‑6, and suppressed the migration of macrophages. Inhibiting expression of miR‑25 may serve a role in upregulating HMGB1 expression, promoting the secretion of inflammatory cytokines and resulting in sepsis.

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