Different modulation of decorin production by lung fibroblasts from patients with mild and severe emphysema.
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.
Noordhoek
Jacobien A
JA
Department of Pulmonology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. j.a.noordhoek@med.umcg.nl
Postma
Dirkje S
DS
Chong
Luis L
LL
Menkema
Lorian
L
Kauffman
Henk F
HF
Timens
Wim
W
van Straaten
Jeanette F M
JF
van der Geld
Ymke M
YM
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
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans