title: Eosinophil cationic protein stimulates TGF-beta1 release by human lung fibroblasts in vitro.
abstract: 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.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. ulrika.zagai@ki.se
authors.forename: Ulrika
authors.initials: U
authors.lastname: Zagai
authors.forename: Elham
authors.initials: E
authors.lastname: Dadfar
authors.forename: Joachim
authors.initials: J
authors.lastname: Lundahl
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.forename: C Magnus
authors.initials: CM
authors.lastname: Sköld
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D047150:Eosinophil Cationic Protein / Q000378:metabolism*; D004804:Eosinophils / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005782:Gels; D006801:Humans; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D005782:Gels; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D003094:Collagen; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human