Exposure to cigarette smoke extract induces proliferation and overexpression of CCL2 in A549 cells and migration in lung fibroblasts

Abstract Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by an aberrant and deregulated remodeling process, where the immune system plays an important role, with smoking being the main risk factor. Cigarette smoke extract (CSE) induces damage and synthesis of cytokines in the epithelium of the respiratory tract. The CCL2 chemokine is elevated in the bronchoalveolar lavage of patients with IPF. However, it is unknown whether CSE induces its profibrotic effect through CCL2. The objective of the study is to evaluate the role of CCL2 in the migration and expression of profibrotic molecules using an In vitro model of A549 lung epithelial cells transfected with the CCL2 gene and CSE-stimulated CCD25 fibroblasts. Our findings indicate that CSE increases the expression of CCL2 and modulates the migration and proliferation of A549 cells and the expression and synthesis of TGF-β1. The conditioned medium of A549 cells that overexpress CCL2 induces migration and overexpression of IL6 in fibroblasts. CCL2 overexpression in CSE-stimulated A549 cells induces a profibrotic effect in CCD25 fibroblasts, serving as an orchestrator in the development of IPF.