MECHANISM OF STIMULATION BY HUMAN INTERFERON OF PROSTAGLANDIN SYNTHESIS IN HUMAN CELL-LINES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (8) , 3209-3214
Abstract
Human interferon .beta.(IFN-.beta.) stimulated the synthesis of prostaglandin E (PGE) and PGF2.alpha. in IFN-sensitive RSa and GM258 cell lines, but not in IFN-resistant HEC-1 cells. IFN-.beta. at a concentration of 1000 U/ml elicited 2- to 3-fold increases in PGE production in these cell lines. In the presence of exogenous arachidonic acid (1 .mu.g/ml), IFN-pretreated cells produced 5-fold more PGE compared to the cell cultures in the absence of arachidonic acid. Prednisolone, an inhibitor of phospholipase A2, at a concentration of 2 .mu.g/ml inhibited the enhanced synthesis of PGE by IFN-pretreated cells. Indomethacin (4 .mu.g/ml), a potent fatty acid cyclooxygenase inhibitor, also inhibited the increased synthesis of PGE. IFN stimulated the release of [14C]arachidonic acid from phospholipids but did not stimulate the activity of fatty acid cyclooxygenase. Thus, IFN evidently stimulates PG synthesis by promoting the release of arachidonic acid from phospholipids. Since cycloheximide and actinomycin D inhibited the stimulation of PGE synthesis, the stimulation of PG synthesis by IFN seemed to be due to de novo enzyme synthesis which catalyzes the release of fatty acid. Addition of exogenous PGE suppressed the growth of RSa and GM258 cells. Prednisolone and iodomethacin partially inhibited anti-cell growth activity of IFN, suggesting a possibility that IFN-inhibited cell growth was partly mediated by PG.