Eosinophil Cationic Protein Stimulates TGF-β₁ Release by Human Lung Fibroblasts In Vitro

Eosinophilic inflammation and airway remodeling are features of asthma. Eosinophil cationic protein (ECP) is released by activated eosinophils and transforming growth factor (TGF)-β₁ has major functions in the fibrotic process. We therefore hypothesized that ECP stimulates TGF-β₁ release by human lung fibroblasts. Fibroblasts in monolayer displayed a constitutive release of TGF-β₁, which increased in presence of ECP (436 ± 60 vs. 365 ± 48 pg/ml at 48 h; P < 0.01). mRNA expression of TGF-β₁ was almost twofold in ECP-stimulated fibroblasts. ECP in three-dimensional cultures stimulated both TGF-β₁ release (180 ± 61 vs. 137 ± 54 pg/ml; P < 0.01) and fibroblast-mediated collagen gel contraction (28 vs. 39% of initial gel area at 48 h; P < 0.001). ECP stimulates TGF-β₁-release by human lung fibroblasts, suggesting a potential mechanism for eosinophils in the fibrotic response. This may be an important mechanism by which ECP promotes remodeling of extra cellular matrix leading to airway fibrosis in asthmatics.