Implications of prostaglandin E2 synthesis and phospholipase C activation in potentiation of T-cell proliferation by LF 1695.
Murine spleen cells, T-enriched by nylon wool filtration, proliferate in the presence of a protein kinase C stimulator and a calcium ionophore. Using this cell proliferation system, we show that LF 1695 can potentiate phorbol myristate acetate (PMA) action in the presence of A 23187. This potentiation can be due to PGE2 inhibition since it is found that lipopolysaccharide (LPS) or A 23187 induced PGE2 release from spleen cells is inhibited by LF 1695. Indomethacin and LF 1695 gave similar stimulation of spleen cell proliferation, and exogeneously added PGE2 inhibits this phenomenon. Considering two of the main early components of intracellular signal transduction, LF 1695 induces IP3 release and calcium mobilization. However, the compound is not mitogenic per se. These results show that LF 1695 behaves only as a costimulant for T-cell proliferation.
Derrepas
P
P
Fournier Laboratories, Research Center 50, Daix, France.
Annat
J
J
Dutartre
P
P
Pascal
M
M
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D010880:Piperidines; D003208:Concanavalin A; D000001:Calcimycin; C046743:LF 1695; D010738:Type C Phospholipases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium