Different Modulation of Decorin Production by Lung Fibroblasts from Patients with Mild and Severe Emphysema

Abstract

We have previously reported diminished immunohistochemical staining of decorin in lung tissue from patients with severe emphysema. The aim of this study is to investigate whether this diminished staining is due to a quantitative abnormal production of decorin by pulmonary fibroblasts in vitro. Therefore, we measured decorin (Western blot), collagen type I (ELISA), and fibronectin (ELISA) production by fibroblasts obtained from lung tissue of patients with severe and mild emphysema at basal culture conditions and after modulation with transforming growth factor-β₁, basic fibroblast growth factor, and interferon-γ. Decorin production at basal culture conditions was significantly higher in fibroblast cultures from patients with severe emphysema compared to fibroblasts from mild emphysema. After stimulation with transforming growth factor-β₁ and basic fibroblast growth factor, decorin production was significantly more reduced in fibroblast cultures from patients with severe emphysema whereas collagen type I and fibronectin production were not affected. We conclude that decorin production by lung fibroblasts of patients with severe emphysema is dysregulated after modulation with cytokines known to be important in smoking associated inflammation. This dysregulation of decorin production may contribute to the impaired lung tissue repair, present in patients with emphysema, since these alterations in the extracellular matrix may cause diminished cytokine binding and neutralization.

• Decorin
• Lung fibroblasts
• Emphysema
• Repair

Abbreviations
bFGF:	=	basic fibroblast growth factor
ECM:	=	extracellular matrix
FCS:	=	fetal calf serum
FEV1:	=	forced expiratory volume in 1 second
IFN-γ:	=	interferon-γ
MMP:	=	matrix metalloproteinases
PI:	=	protease inhibitor
TGF-β1:	=	transforming growth factor-β1
VC:	=	vital capacity