Lunasin influences macrophage–pulmonary epithelial crosstalk in cellular model of hypersensitivity pneumonitis

Introduction and Objective.Hypersensitivity pneumonitis (HP) is a chronic immune-mediated interstitial lung disease driven by persistent antigen exposure, macrophage activation, and progressive lung remodelling.Macrophage-derived transforming growth factor beta (TGF-β) plays a key role in epithelial-mesenchymal transition (EMT), contributing to fibrosis development.Lunasin, a soybean-derived bioactive peptide, exhibits anti-inflammatory and immunomodulatory properties, but its influence on macrophage-epithelial interactions in HP remains unclear.The aim of the study is to evaluate the effects of lunasin on antigen-induced macrophage activation, TGF-β secretion, and macrophage-driven EMT in a long-term in vitro model of HP. Materials and Method.SC macrophages were chronically stimulated with Pantoea agglomerans antigen in the presence or absence of lunasin (50 µM).Viability (MTT), macrophage polarization (flow cytometry), and TGF-β secretion (CBA assay) were assessed.NL20 bronchial epithelial cells were exposed to macrophage-conditioned media, and morphological changes and EMT marker expression were analyzed.Results.Lunasin attenuated antigen-induced M1 polarization at later time points but did not significantly alter TGF-β levels in PA-stimulated macrophages.Conditioned media from antigen-activated macrophages induced EMT-like changes in epithelial cells, including altered morphology and increased mesenchymal marker expression.Media derived from lunasin-treated macrophages partially preserved epithelial morphology and produced limited, marker-specific changes in EMT-associated proteins.Conclusions.Lunasin modulates antigen-induced macrophage activation and influences macrophage-epithelial crosstalk in vitro, attenuating selected profibrotic and EMT-associated responses relevant to HP-related lung remodelling.