title: Heparin and PGE2 inhibit DNA synthesis in human airway smooth muscle cells in culture.
abstract: An increase in the bulk of the airway smooth muscle is a characteristic of asthma. Much of the research investigating the mechanisms of this increase in muscle has focused on mediators that are mitogenic for smooth muscle, while relatively few studies have focused on mediators inhibiting mitogenesis. In this study we have examined the effects of two mediators proposed as regulators of smooth muscle proliferation, namely heparin and prostaglandin (PG) E2, on human airway smooth muscle cells in culture stimulated with 1, 2.5, 5, and 10% fetal bovine serum (FBS) and platelet-derived growth factor AB (PDGF), 50 ng/ml. PGE2 had a biphasic effect on DNA synthesis in the presence of 1% FBS, with 10(-6) M causing inhibition and 10(-7) M causing an increase in DNA synthesis. PGE2 caused inhibition of DNA synthesis in the presence of 2.5, 5, and 10% FBS. Heparin (10 and 100 U/ml) caused an inhibition of DNA synthesis induced by 1% FBS, while 100 U/ml inhibited DNA synthesis induced by 5 and 10% FBS. PGE2 (10(-8), 10(-7), and 10(-6) M) inhibited the DNA synthesis induced by PDGF, while heparin (1, 10, and 100 U/ml) had no effect. These results indicate that both PGE2 and heparin may have a role in the control of human airway smooth muscle cell growth.
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002417:Cattle / Q000097:blood / Q000196:embryology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology
chemical_list: D010982:Platelet-Derived Growth Factor; D006493:Heparin; D004247:DNA; D015232:Dinoprostone