Prostaglandin E2 inhibition of growth in a colony-stimulating factor 1-dependent macrophage cell line.
The effects of prostaglandin E2 (PGE2) were examined in a murine macrophage cell line (BAC1.2F5) that was completely dependent on colony-stimulating factor-1 (CSF-1) for both growth and survival. The addition of PGE2 to cultures of BAC1.2F5 cells resulted in the inhibition of CSF-1-induced [3H]thymidine incorporation and cell proliferation. The inhibitory effects of PGE2 were mimicked by the addition of dibutyryl-cyclic AMP, and the effectiveness of PGE2 was markedly potentiated by 1-methyl-3-isobutylxanthine, a potent inhibitor of cyclic nucleotide phosphodiesterase activity. PGE2 caused a 10-fold elevation of the intracellular cyclic AMP concentration, whereas CSF-1 neither increased cyclic AMP levels nor attenuated the rise in cyclic AMP promoted by PGE2. However, CSF-1 may indirectly regulate cyclic AMP levels since in the absence of CSF-1, BAC1.2F5 cells actively synthesized PGE2, whereas PGE2 production was abruptly terminated by the addition of CSF-1. In BAC1.2F5 cells, PGE2 increases the intracellular cyclic AMP concentration, thereby blocking cell proliferation, but does not down-regulate the CSF-1 receptor or abrogate the functions of CSF-1 necessary for cell survival.
Jackowski
S
S
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Rettenmier
C W
CW
Rock
C O
CO
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D003115:Colony-Stimulating Factors; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D016173:Macrophage Colony-Stimulating Factor; D015232:Dinoprostone; D013936:Thymidine