CEBPB inhibition via miRNA298-5p mediates inflammation in ARDS 3885

Abstract Description Acute Respiratory Distress Syndrome (ARDS) poses a significant risk in advanced COVID-19 and other inflammatory conditions. Characterized by damage to the pulmonary endothelium and epithelium, leading to pulmonary edema, hypoxemia, and excessive inflammation. This study investigates the therapeutic effects of cannabidiol (CBD) in reducing inflammatory responses in ARDS through miRNA-mediated pathways. The cytokine storm in severe COVID-19 can be modeled using Staphylococcus enterotoxin B (SEB). Single-cell RNAseq revealed that CBD reduced inflammatory macrophage infiltration while enhancing T regulatory (Treg) activity. Here, we explore the molecular mechanisms behind CBD’s anti-inflammatory effects, focusing on miRNA 298-5p, a key regulator of CEBPB, a transcription factor central to pro-inflammatory pathways like NF-kB and IL-6. In vivo studies showed that CBD administration (5 mg/kg) elevated miRNA 298-5p expression and inhibited CEBPB activity. This led to decreased levels of IL-6, TNF-α, and Th17 cells, while promoting Tregs and M2 macrophages that enhance tissue repair through increased IL-10 production, and dampening inflammation. In vitro experiments using miRNA mimics and inhibitors, along with CEBPB agonists and antagonists, clarified the inflammatory effects of CEBPB in splenocytes. Overall, these findings underscore CBD’s potential, via miRNA 298-5p modulation, as an effective therapeutic strategy for alleviating hyperinflammation and fostering immune resolution. Funding Sources Supported by: NIH R00GM147910 Topic Categories Immune Mechanisms of Human Disease (HUM)