Eosinophil cationic protein stimulates TGF-beta1 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)-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.
Zagai
Ulrika
U
Division of Respiratory Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. ulrika.zagai@ki.se
Dadfar
Elham
E
Lundahl
Joachim
J
Venge
Per
P
Sköld
C Magnus
CM
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*
D005782:Gels; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D003094:Collagen; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human