Knockdown of Slfn5 alleviates lipopolysaccharide-induced pneumonia by regulating Janus kinase/signal transduction and activator of transcription pathway.

Abstract

In recent years, the incidence of pneumonia has been increasing, which is the main cause of death and morbidity of children and the elderly in the world. Slfn5 is implicated in multiple cancers, and Slfn5 promotes epithelial-mesenchymal transition and metastasis in lung cancer. However, the influences of Slfn5 in pneumonia have not yet been completely cleared. Herein, we aimed to explore the underlying effects and regulatory mechanisms of Slfn5 in lipopolysaccharide (LPS)-induced pneumonia in mice and A549 cells. Mice were intratracheally administered 5 mg/kg LPS to construct pneumonia model. In vitro, A549 cells were treated with 10 µg/mL LPS to construct cellular pneumonia model. Slfn5 expression was detected using immunohistochemistry and western blotting. Haematoxylin and eosin staining, TUNEL (terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate‑biotin nick end‑labelling), and western blotting were performed to assess pathological injury and inflammation. MTT [3(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2‑H‑tetrazolium bromide], flow cytometry, and enzyme-linked immunosorbent assay analysis were performed to analyze cell viability, apoptosis, and inflammation. Gene set enrichment analysis was performed to explore the mechanism of Slfn5 in pneumonia. Slfn5 expression was upregulated in LPS-induced pneumonia in mice and A549 cells. In mice, knockdown of Slfn5 weakened LPS-induced lung injury and inflammation and decreased the expression of p-JAK2, p-JAK3, and p-STAT3. In LPS-stimulated A549 cells, downregulation of Slfn5 expression increased and Slfn5 overexpression decreased cell viability. Downregulation of Slfn5 expression decreased and Slfn5 overexpression increased cell apoptosis, inflammation and the expression of p-JAK2, p-JAK3, and p-STAT3. AG490, an inhibitor of the JAK/STAT pathway, reversed the damaging effects of Slfn5 overexpression. In the LPS-induced pneumonia model, Slfn5 knockdown alleviated LPS-induced lung injury by regulating the JAK/STAT pathway.