Eosinophilic inflammation and airway remodeling are features of asthma. Eosinophil cationic protein (ECP) is released by activated eosinophils and transforming growth factor (TGF)-beta(1) has major functions in the fibrotic process. We therefore hypothesized that ECP stimulates TGF-beta(1) release by human lung fibroblasts. Fibroblasts in monolayer displayed a constitutive release of TGF-beta(1), which increased in presence of ECP (436 +/- 60 vs. 365 +/- 48 pg/ml at 48 h; P < 0.01). mRNA expression of TGF-beta(1) was almost twofold in ECP-stimulated fibroblasts. ECP in three-dimensional cultures stimulated both TGF-beta(1) 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-beta(1)-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.