Prostacyclin analogs inhibit fibroblast migration.
The controlled accumulation of fibroblasts to sites of inflammation is crucial to effective tissue repair after injury. Either inadequate or excessive accumulation of fibroblasts could result in abnormal tissue function. Prostacyclin (PGI(2)) is a potent mediator in the coagulation and inflammatory processes. The aim of this study was to investigate the effect of PGI(2) on chemotaxis of human fetal lung fibroblasts (HFL-1). Using the blind well chamber technique, we found that the PGI(2) analog carbaprostacyclin (10(-6) M) inhibited HFL-1 chemotaxis to human plasma fibronectin (20 microg/ml) 58.0 +/- 13.2% (P < 0.05) and to platelet-derived growth factor (PDGF)-BB (10 ng/ml) 48.7 +/- 4.6% (P < 0.05). Checkerboard analysis demonstrated that carbaprostacyclin inhibits both directed and undirected migration. The inhibitory effect of the carbaprostacyclin was concentration dependent and blocked by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, suggesting that a cAMP-PKA pathway may be involved in the process. Two other PGI(2) analogs, ciprostene and dehydro-15-cyclohexyl carbaprostacyclin (both 10(-6) M), significantly inhibited fibroblast migration to fibronectin. In summary, PGI(2) appears to inhibit fibroblast chemotaxis to fibronectin and PDGF-BB. Such an effect may contribute to the regulation of fibroblasts in wound healing and could contribute to the pathogenesis of diseases characterized by abnormal tissue repair remodeling.
Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5125, USA.
Tadashi
T
Kohyama
Xiangde
X
Liu
Hui Jung
HJ
Kim
Tetsu
T
Kobayashi
Ronald F
RF
Ertl
Fu-Qiang
FQ
Wen
Hajime
H
Takizawa
Stephen I
SI
Rennard
D000077214:Becaplermin; D002227:Carbazoles; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005347:Fibroblasts / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000196:embryology; D009994:Osmolar Concentration; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011758:Pyrroles / Q000494:pharmacology
D002227:Carbazoles; D004791:Enzyme Inhibitors; D005353:Fibronectins; D007211:Indoles; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011758:Pyrroles; C462339:dehydro-15-cyclohexylcarbaprostacyclin; D000077214:Becaplermin; C057416:KT 5720; D011464:Epoprostenol; D017868:Cyclic AMP-Dependent Protein Kinases; C045329:ciprostene