Exploring the mechanism of interleukin-24 in regulating eosinophil differentiation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) exacerbation is a common respiratory condition, particularly when accompanied by eosinophilia, which mediates inflammatory responses that significantly impair the integrity of the airway mucosal barrier. This study aims to elucidate the roles of interleukin-24 (IL-24) and eosinophils (EOS) in COPD-associated tissue remodeling, focusing on their effects on the expression of pro-inflammatory mediators and extracellular matrix (ECM) components in pulmonary fibroblasts, as well as the underlying molecular mechanisms. Based on the differential expression of IL-24 between healthy individuals and COPD patients and its correlation with EOS, we differentiated EOL-1 cells into EOS using butyrate and established a co-culture system with pulmonary fibroblasts. Concurrently, groups of fibroblasts were stimulated with varying concentrations of IL-24 alone. The regulatory effects on pro-inflammatory mediators and ECM expression were systematically analyzed using flow cytometry, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and Western blotting. Under the present experimental conditions, IL-24 treatment was associated with enhanced fibrotic responses in pulmonary fibroblasts. Furthermore, compared with butyrate treatment alone, the combination of IL-24 and butyrate further increased the differentiation rate of EOL-1 cells into EOS cells. Differentiated EOS further stimulated pulmonary fibroblasts to secrete pro-inflammatory factors IL-6 and IL-8, as well as the tissue remodeling-related factor vascular endothelial growth factor (VEGF), thereby exacerbating the fibrotic process. This study confirms that IL-24 promotes the maturation and differentiation of EOL-1 cells and can induce a fibrotic phenotypic transformation in pulmonary fibroblasts. This interaction participates in regulating inflammatory responses and tissue remodeling during COPD progression, highlighting the critical role of eosinophil-fibroblast crosstalk in the pathological mechanisms of the disease.