MicroRNA‑23a‑3p targeting of HMGB1 inhibits LPS‑induced inflammation in murine macrophages in vitro

Abstract

Inflammatory cytokines, including high mobility group box 1 (HMGB1), play a key role in sepsis via various mechanisms, some of which remain unknown. Sepsis is a common cause of death in patients admitted to the intensive care unit. MicroRNAs (miRs) serve an important role in the inflammatory response. The present study aimed to investigate the role of miR-23a-3p in macrophage inflammation and the targeted regulation of HMGB1 expression. The murine macrophage cell line RAW264.7 was subjected to lipopolysaccharide (LPS) treatment to mimic the inflammation involved in sepsis in vitro. Reverse transcription-quantitative PCR was performed to measure miR-23a-3p expression and mRNA expression. Protein levels were determined using ELISA and western blotting. The target binding relationship between miR-23a-3p and the HMGB1 3'untranslated region was predicted and validated with a dual luciferase reporter assay. HMGB1 expression was increased and miR-23a-3p expression significantly reduced in patients with sepsis and in LPS-treated RAW264.7 cells in comparison with controls. Overexpression of miR-23a-3p reduced interleukin (IL)-6 and tumor necrosis factor (TNF)-α expression in RAW264.7 cells under LPS stimulation, while silencing of miR-23a-3p elevated the expression of IL-6 and TNF-α in comparison with controls. The inhibitory effect of miR-23a-3p on LPS-induced inflammation could be abolished by HMGB1 upregulation in RAW264.7 cells. HMGB1 was targeted by miR-23a-3p. miR-23a-3p is expressed at reduced levels during inflammation in sepsis, and overexpression of miR-23a-3p inhibits LPS-induced inflammation in murine macrophages in vitro by directly downregulating HMGB1. The results of the present study provided a novel insight into the molecular mechanism underlying HMGB1 expression at the post-transcriptional level in sepsis.

ATP2B1-AS1 exacerbates sepsis-induced cell apoptosis and inflammation by regulating miR-23a-3p/TLR4 axis

“…MiR-23a-3p has been revealed to be downregulated in LPS-treated RAW264.7 cells and patients with sepsis. 33 More importantly, miR-23a-3p has been highlighted to be sponged by different lncRNAs to take part in a variety of diseases. For instance, lncRNA PAHRF sponges miR-23a-3p to mediate proliferation and apoptosis in pulmonary arterial hypertension.…”

Anti-Inflammatory Potency of Human Wharton’s Jelly Mesenchymal Stem Cell-Derived Exosomes on L2 Cell Line Induced by Lipopolysaccharides

“…Furthermore, decreased NF-κB activity measured by p65 levels decreases IL-1β, TNF-α, and IL-6 levels and lung tissue damage. 28 The protein present in nor-exo and hypo-exo also has a biological pathway. Under hypoxic conditions, MSCs enriched their cargo with anti-inflammatory cytokines and angiogenesis-related proteins as mentioned in De Jong et al 29 Overall, the results of this study can be summarized in several points.…”