J. Biol. Chem., Vol. 265, Issue 12, 6611-6616, Apr, 1990
Prostaglandin E2 inhibition of growth in a colony-stimulating factor 1- dependent macrophage cell line
S Jackowski, CW Rettenmier and CO Rock
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
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.