Effect of exogenous prostaglandins and nonsteroidal anti-inflammatory agents on prostaglandin secretion and proliferation of mouse embryo fibroblasts in culture.
During wound healing, the positive and negative modulation of fibroblast proliferation may be due, in part, to the high prostaglandin concentration of the inflammatory exudates. In vitro, PGF2 alpha has been shown to stimulate, whereas PGE2 inhibits, the growth of different fibroblast cell lines. Therefore, we have investigated the effect of exogenous prostaglandins (PGs) and of various nonsteroidal anti-inflammatory drugs (NSAIDs) on the proliferation and the prostaglandin (PG) synthesis of normal mouse embryo fibroblasts. PGF2 alpha, 6-keto PGF1 alpha and PGE2 increase fibroblast proliferation. On the other hand, PGF2 alpha increases the synthesis of PGE2 and 6-keto PGF1 alpha while 6-keto PGF1 alpha solely inhibits PGF2 alpha release, PGE2 being inactive. The mouse embryo fibroblasts partially transform the prodrug sulindac sulfoxide in the sulfide form, which completely inhibits PG synthesis, as does indomethacin. In contrast, ibuprofen exerts a differential action, according to the type of PG measured. Among the NSAIDs tested, only sulindac (sulfoxide or sulfide) stimulates fibroblast proliferation and this effect appears independent of an alteration of PG synthesis. Therefore, in this model of normal mouse embryo fibroblasts, while endogenous prostaglandins are not involved in the control of cell proliferation, exogenous PGs have the ability to alter fibroblast growth and PG synthesis.
Durant
S
S
INSERM U7, Hôpital Necker, Paris, France.
Duval
D
D
Homo-Delarche
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000493:pharmacokinetics; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015237:Dinoprost / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone