title: 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-beta1, basic fibroblast growth factor, and interferon-gamma. 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-beta1 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.
authors.affiliation: Department of Pulmonology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. j.a.noordhoek@med.umcg.nl
authors.forename: Jacobien A
authors.initials: JA
authors.lastname: Noordhoek
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Luis L
authors.initials: LL
authors.lastname: Chong
authors.forename: Lorian
authors.initials: L
authors.lastname: Menkema
authors.forename: Henk F
authors.initials: HF
authors.lastname: Kauffman
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Jeanette F M
authors.initials: JF
authors.lastname: van Straaten
authors.forename: Ymke M
authors.initials: YM
authors.lastname: van der Geld
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000096:biosynthesis*; D011656:Pulmonary Emphysema / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans