Alveolar Fibroblasts Respond to <i>Pseudomonas Aeruginosa</i> Infection With Cytokine Secretion: Role in Acute Lung Inflammation

ABSTRACT Alveolar fibroblasts play a key role in regulation of lung inflammation. Pseudomonas aeruginosa (PAO) is one of the most common pathogens causing lung injury, and the role of PAO‐infected alveolar fibroblasts in such a condition remains unclear. The tumor necrosis factor (TNF)‐α was significantly upregulated in alveolar fibroblasts with PAO‐associated lung injury patients. Alveolar fibroblasts infected with PAO, combined with gene expression profiling, revealed elevated levels of pro‐inflammatory cytokines, and this finding was closely linked to neutrophil‐mediated inflammatory injury. Gene Ontology and Kyoto Encyclopedia of Genes Genomes enrichment analysis indicated that differentially expressed genes were linked to pro‐inflammatory signals, including necroptosis, nuclear factor (NF)‐κB inflammatory signaling, pro‐inflammatory cytokine production, and neutrophil migration/activation. Furthermore, Western blot and enzyme‐linked immunosorbent assay results demonstrate that PAO activated the NF‐κB pathway and enhanced the expression and secretion of pro‐inflammatory cytokines in alveolar fibroblasts. The study findings suggest that PAO‐infected alveolar fibroblasts contribute to the development of pulmonary inflammatory injury.