Effects of dexamethasone on proliferation, chemotaxis, collagen I, and fibronectin-metabolism of human fetal lung fibroblasts.
Premature infants at risk for bronchopulmonary dysplasia (BPD) are often treated with dexamethasone (Dex), which has been shown to suppress inflammatory processes in the lung. To elucidate a possible direct influence on the fibroproliferative component of the disease, we studied the effects of Dex in therapeutic and supratherapeutic dosages (5-50 nmol/L) on proliferation, chemotaxis, procollagen I, and fibronectin metabolism of human fetal lung fibroblasts in vitro. Proliferation was inhibited by Dex in a dose-dependent manner. Chemotactic activity in response to conditioned medium of human fetal fibroblasts also showed a dose-dependent inhibition after pretreatment with Dex. The amount of procollagen I C-terminal propeptide and fibronectin per cell in the cell culture supernatant was increased in the presence of Dex. Our results show that Dex does not uniformly suppress the fibroproliferative activity of human fetal lung fibroblasts, which may explain in part the unsatisfactory long-term effects of Dex treatment in BPD.
Brenner
R E
RE
Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedics, University of Ulm, Ulm, Germany. rolf.brenner@medizin.uni-ulm.de
Felger
D
D
Winter
C
C
Christiansen
A
A
Hofmann
D
D
Bartmann
P
P
D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000031:analogs & derivatives / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D005353:Fibronectins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D055370:Lung Injury; D011247:Pregnancy; D011347:Procollagen / Q000187:drug effects* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005353:Fibronectins; D011347:Procollagen; D003907:Dexamethasone; D003094:Collagen