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.
Key wordsairway remodeling ECP eosinophil fibroblast TGF-β
The authors would like to thank Professor Rolf Lewensohn at the Cancer Centrum Karolinska, for letting us use equipment for DNA analysis and Per Näsman at the Royal Institute of Technology, for assistance with statistical analysis. For the preparation and characterization of ECP the work of Lena Moberg and Agneta Trulson is greatly appreciated. The financial support from the Swedish Heart–Lung Foundation, Cancer and Allergy Foundation, Swedish Foundation for Health Care Science and Allergy Research, Hesselman Foundation, Boehringer-Ingelheim/Pfizer, the Swedish Research Council and Karolinska Institutet is greatly appreciated.
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